Diagnostic markers of immunosenescence and methods of use thereof

ABSTRACT

Embodiments of the present invention provide diagnostic markers of immunosenescence and methods of identifying individuals with impaired immune function based on a combination of such markers obtained from various analyses, primarily from blood, testing immune function including the analysis of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines (‘cytokine response’). Particular combinations of markers can predict with high accuracy whether an individual will respond to active vaccination and become protected against recurring diseases.

RELATED APPLICATION

This application claims priority and other benefits from U.S. Provisional Patent Application Ser. No. 61/358,884, filed Jun. 25, 2010, entitled “Methods of identifying individuals with impaired immune function”. Its entire content is specifically incorporated herein by reference.

STATEMENT OF GOVERNMENT SUPPORT

This invention was made with government support under U19 AI057229 awarded by the National Institutes of Health. The government has certain rights in the invention.

BACKGROUND

Deterioration of immune function is a prominent hallmark of aging and is only partially explainable by a loss of naïve and central memory CD4 T cells due to thymic involution. Defects in both the innate and adaptive immune system of the elderly have been described and include changes in immune cell-subsets abundance and relative frequencies, altered hematopoiesis, impairments in antigen presentation, decreased B cell as well as T cell proliferation, a reduced TCR repertoire and defect in antibody production (Weiskopf et al., 2009). Ultimately these alterations result in a sharp decline in the response to new and persisting antigens (immunosenescence). Thus it is not surprising that infectious diseases are one of the major causes of mortality in those over the age of 65 and that protective vaccination of the elderly is more difficult to establish than in younger individuals (Goodwin, 2006).

Active immunization and activation of T cell-mediated as well as humoral immune response can be achieved through the administration of immunogenic material or vaccines. Vaccination seeks to prevent, ameliorate or even treat against the harmful effects of pathogens and carcinogens, and regular vaccination has become an integral part of preventive medicine.

Due to the complexity of the immune system, studies of immunosenescence often only investigate one or a few variables of an individual's immune system. This has made it difficult to draw general conclusions about the phenomena being described or how they might relate to each other. Individuals who suffer from an impaired immune function generally face the risk of increased morbidity and mortality. This is particularly relevant for older individuals who show a reduced response to vaccination or have persistent cytomegalovirus infection (Strindhall et al., 2007). The immune system of those individuals can be phenotypically characterized as having an inverted CD4+to CD8+ T-cell ratio (below one), and a high frequency of CD8+CD28− T-cells (Wikby et al., 2008). There is also evidence that other major causes of mortality in older individuals, such as cardiovascular diseases, cancer and Alzheimer's disease, might involve defects in normal immune function (Hansson, 2005; de Visser et al., 2006; Rojo et al., 2008). This raises the possibility that a functional immune response is a key factor in the maintenance of good health and longevity.

One of the most challenging topics facing the maintenance of good health and longevity is the identification of immunocompromised individuals who might appear healthy, but who have an underlying, undetected impairment of immune function and, so, face the risk of increased morbidity and mortality. The present invention addresses this issue.

SUMMARY

Embodiments of the present invention provide diagnostic markers of immunosenescence and methods of identifying individuals with impaired immune function based on a combination of such markers obtained from various analyses, primarily from blood, testing immune function including the analysis of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines (‘cytokine response’). Particular combinations of markers can predict with high accuracy whether an individual will respond to active vaccination and become protected against recurring diseases.

The above summary is not intended to include all features and aspects of the present invention nor does it imply that the invention must include all features and aspects discussed in this summary.

INCORPORATION BY REFERENCE

All publications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

DRAWINGS

The accompanying drawings illustrate embodiments of the invention and, together with the description, serve to explain the invention. These drawings are offered by way of illustration and not by way of limitation; it is emphasized that the various features of the drawings may not be to-scale.

FIG. 1: Phosphorylation of STATs in response to cytokine stimulation drops with age. (A) Heat map of 72 cytokine stimulation assays measured across 29 individuals of different ages. Each assay measures the fold-change phosphor-STAT-1, -3 or -5 in one of four immune cell subsets (B-cell, CD4 T-helper cells, CD8 cytotoxic T cells and monocytes) stimulated by one of six cytokines (IFN-α, IFN-γ, IL6, IL7, IL10 and IL21) and measured by flow cytometry. Each assay appears in a single row and is color coded (left of heatmap) by the condition (cell subset, cytokine, pSTAT combination) (see legend on top). Coloring of the heat map cells reflects the normalized fold-change z-scores, that is, the number of standard deviations from the population mean of the assay. Age-associated differences at a (q≦0.15) are marked on right (red decrease with age, purple, increase; grey, no significant difference). (B) Example scatter plot illustrating the reduced fold-change response of some older individual in CD4⁺ T cells stimulated by IL6 and assayed for STAT-3 phosphoprylation. (C) Baseline phosphoSTAT levels increase with age. Shown are normalized z-scores. (D) Reduced cellular response in old individuals is independent of stimulus concentration. The entire 72-condition cytokine response assay was repeated at five different doses per stimuli for two young and two older individuals, whose average fold-change response to cytokine stimulation was respectively high or low. Shown is an example histogram (left) and line plot visualization (right) of the fold-change cytokine response as a function of cytokine stimuli concentration for each of the two young (black) and two old (cyan) individuals. A fold change of 1 signifies no change from baseline. The young individuals show a significantly higher fold-change response than that observed in old individuals, at all concentrations (See Fig. S4 for all other assays). (E) A general reduction in cytokine responses is observed with age with some individuals showing systemic impairments in multiple assays. The y-axis plots the sum of z-scores all 39 age-associated responses.

FIG. 2: Systemic impairments in cytokine responses with age co-occur in a single individual with dysfunctional immune cell subsets and increased inflammation. (A) Age associated cytokine response deficiencies correlate with known cell subset immunosenescence markers such as the drop CD4⁺ and CD8⁺ naïve cell frequency, and known serum chemokine changes with age, but as measured in serum, not with cytokines such as IL-6 and IL-1 that are proinflammatory and known to rise with age. (B) Biological validation of increased pro-inflammatory cytokine environment at baseline in sorted monocytes of two cytokine stimulation non-responsive older individuals (cyan) compared to two young individuals (orange). (C) Sparse canonical correlation analysis identifies a module of network nodes whose weighted linear combination is maximally correlated with the cytokine response deficiency of a given cell type. The normalized weights of each cell's maximally correlated module are shown in a bar plot format (grayscale), sorted by the weights of the module maximally correlated with B-cell cytokine response.

FIG. 3: Cytokine responses define distinct age-related subgroups that are longitudinally stable. (A) Individuals are stratified as CR (green), CNR (blue) or an intermediate phenotype (purple) by scoring the number of cell-types for that individual in which significant impairment was observed compared with the mean of the young. (B) A longitudinal study of cytokine non-response (cytokine deficiency) in 21 returning individuals. Cytokine response state is stable or worsen with time (p<0.02). Shown are cytokine response class (top) or cell state (bottom) for baseline (year 1) and two subsequent years.

FIG. 4: Cytokine responder and non-responder older individuals have distinctly different immune system profiles. (A) The young and the CR group show more robust pre-vaccination antibody titer levels, compared with the CNR when considered simultaneously across all strains. At the population level, an antibody titer of 1:30-1:40 (above 5 on log₂ scale) represents probability of 50% protection against Influenza infection. Standard errors are shown. (B) Heatmap showing the association between immune system state and longevity. The z-score normalized expression of the top 60 longevity-associated genes from GenAge that are differentially expressed between CR and CNR (out of 159). Shown are all older individuals. Colored boxes on top reflect their cytokine response classification and the specific cells in which their response was reduced. Two distinct clusters of CR and CNR are observed with additional individuals clustering in CR. Genes are clustered by pathway membership (matrix on right).

FIG. 5. Stratification of older individuals by cytokine response yields increased resolution to age dependent changes. (A) Venn diagram summarizing the number of identified markers for each of the CR and CNR-specific signatures, as well as those changes that occur, independent of cytokine responses, with age. (B) Differing proportions of CR and CNR older individuals in aging studies may explain many of the controversies in the immunosenescence literature. Examples highlight changes in age which either exclusive for both CR and CNR or common to both. Distinct: changes in the frequency of Eotaxin, NKT cells and B cells that are masked by the heterogeneity of older individuals. Common: The reduction in CD8⁺ naïve cells is common to all older individuals, though much more dramatic in CNR. Standard errors are shown.

FIG. 6: Reduced responses to cytokine stimulation are primarily due to increased basal levels of phosphorylated STAT proteins and to alterations in response potential of IL6 and IFNα pathways. (A) Top: Four model classes which may yield the observed unresponsive cells phenotype: (1) successful adaptation to increased background abundance of cytokines, (2) a resistance defect in the signaling machinery of cells from older individuals, (3) an increase in baseline pSTAT levels, which may yield a reduced fold-change response to stimulation by exhausting finite quantities of protein to phosphorylate (4) a combination of both baseline and resistance defect factors. Bottom: Each age-associated cytokine responses deficiencies is classified into one of the four models using a decision tree. No adaptation is observed. Only the monocyte stimulations could be classified solely as a resistance defect. The rest all showed a significant elevation in the older individuals' baseline pSTAT levels, with IL6 and IFNα also showing defects in resistance pathways. (B) Inverse relationship between normalized baseline phosphoprotein abundance of pSTAT1 in CD8 cells (X-axis) and normalized fold-change response to stimulation by IFNα (Y-axis). Older individuals show a higher baseline level of pSTAT1 with a decreased response. (C) A cartoon model illustrating the queries used to discriminate between the different models of immune cells unresponsiveness.

Figure S1: Study schematic design—‘One stop shop’ multi-level biological analysis of blood from subjects of different age groups & gender

Figure S2: Immune cell subset gating scheme.

Figure S3: Number of measurements called significantly associated with age as a function of false discovery rate. Gene expression studies focused primarily on the immune and aging associated 2863 genes on the array which are measured by 4364 probes.

Figure S4: Reduced cellular response in the elderly is not concentration dependent. Shown are all dose-response curves for the 72 assays performed between young (grey) and old (cyan).

Figure S5: The majority of age-associated cytokine responses reach saturation in both young and older subjects at the highest concentration level. The standard deviation of the two last points in the dose response curve was calculated and visualized in a heatmap format. Very few of the assays are still changing significantly. Shown are all assays in which a fold-change response ≧2 is observed in atlast one concentration in one or more subjects.

Figure S6: Cytokine stimulation responses by cell-type used to define CR and CNR. Sum of z-score normalized age-associated cytokine stimulation responses by cell-type. Dashed black line is the average of the young subjects. Dashed red line is 2 standard deviations from the young average. The IDs of olde subject subjects are listed for each cell-type.

Figure S7: HAI titers grouped by cytokine responses. Titer levels pre and post vaccine grouped by response category and strain in vaccine. Seroprotection is clinically defined as a value of ˜5 on this scale and seroconversion as a four-fold of higher change.

Figure S8: Number of measurements called significantly different between CR and CNR as a function of false discovery rate.

Figure S9: The “Immune Risk Profile” of inverted CD4/CD8 (<1) ratio is not age specific and is highly variable. Though correlated, an inverted CD4/CD8 ratio is not specific or required for systemic impairments in cytokine responses. Shown is the ratio of CD4 to CD8 frequency as a function of the sum of all age-associated cytokine response assays. Young, CR, CNR and Intermediates are colored by their cytokine response class in year 1 in organge, green, purple or blue respectively.

Figure S10: Number of measurements called significantly different between CR and the young and CNR and the young as a function of false discovery rate.

Figure S11: Detailed classification of age-associated changes by cytokine response. Venn diagram illustrating the identified markers for each of the CR and CNR specific signatures, as well as those changes that occur, independent of cytokine responses, with age. For gene expression and statistics, see Table S7-S9.

Figure S12: An Inverse relationship between normalized baseline phosphoprotein abundance and fold-change. Shown are only those 39 assays for which an age-associated difference was detected in the data. Normalized Fold-change response on the Y axis, normalized baseline on the X.

Figure S13: Classification of cytokine response deficiency by cause. A decision tree over the cytokine response fixed dose and dose-response assays can discriminate between the different models of immune cells unresponsiveness. Shown are the decision tree classification for all age-associated cytokine responses as identified from the entire study population. No adaptation is observed. Only the monocyte stimulations could be classified solely as a resistance defect. The rest all showed a significant elevation in the older subjects' baseline pSTAT levels, with IL6 and IFNα also showing defects in resistance pathways.

Table S1: Study design demographics

Table S2: Significant age-associated measurement from regression analysis of all subjects.

Table S3: GEO Datasets used in meta-analysis of aging gene expression data. Table lists all GSM data ids used for comparisons.

Table S4: Genes found to be significantly associated with age in the meta-analysis.

Table S5: Network cluster membership.

Table S6: Cytokine response modules feature weights

Table S7: Significant differences between CR and CNR.

Table S8: Medication category listing for CR and CNR.

Table S9: Age-associated differences common to both CR and CNR,

Table S10: CR-specific measurements.

Table S11: CNR-specific measurements.

Table S12: Dose-response classification results.

DEFINITIONS

The practice of the present invention may employ conventional techniques of chemistry, molecular biology, recombinant DNA, microbiology, cell biology, immunology and biochemistry, which are within the capabilities of a person of ordinary skill in the art. Such techniques are fully explained in the literature. For definitions, terms of art and standard methods known in the art, see, for example, Sambrook and Russell ‘Molecular Cloning: A Laboratory Manual’, Cold Spring Harbor Laboratory Press (2001); ‘Current Protocols in Molecular Biology’, John Wiley & Sons (2007); William Paul ‘Fundamental Immunology’, Lippincott Williams & Wilkins (1999); M. J. Gait ‘Oligonucleotide Synthesis: A Practical Approach’, Oxford University Press (1984); R. Ian Freshney “Culture of Animal Cells: A Manual of Basic Technique’, Wiley-Liss (2000); ‘Current Protocols in Microbiology’, John Wiley & Sons (2007); ‘Current Protocols in Cell Biology’, John Wiley & Sons (2007); Wilson & Walker ‘Principles and Techniques of Practical Biochemistry’, Cambridge University Press (2000); Roe, Crabtree, & Kahn ‘DNA Isolation and Sequencing: Essential Techniques’, John Wiley & Sons (1996); D. Lilley & Dahlberg ‘Methods of Enzymology: DNA Structure Part A: Synthesis and Physical Analysis of DNA Methods in Enzymology’, Academic Press (1992); Harlow & Lane ‘Using Antibodies: A Laboratory Manual: Portable Protocol No. I’, Cold Spring Harbor Laboratory Press (1999); Harlow & Lane ‘Antibodies: A Laboratory Manual’, Cold Spring Harbor Laboratory Press (1988); Roskams & Rodgers ‘Lab Ref: A Handbook of Recipes, Reagents, and Other Reference Tools for Use at the Bench’, Cold Spring Harbor Laboratory Press (2002); Alon U (2007). An introduction to systems biology: design principles of biological circuits (Boca Raton, Fla.: Chapman & Hall/CRC). Each of these general texts is herein incorporated by reference.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art to which this invention belongs. The following definitions are intended to also include their various grammatical forms, where applicable.

The term “impaired immune function”, as used herein, refers to any reduction in immune function in an individual, as compared to a fully healthy individual. Individuals with an impaired immune function are readily identifiable by substantially increased abundance of CD8+ CD28− cells or more broadly by reduced cytokine responses, increased baseline phosphoprotein levels and other co-occurring measures.

The term “older individual”, “elderly individual” or “elderly”, as used herein, defines a human being who is about 60 years of age or older.

The term“young individual”, as used herein, defines a human being between 18 and 30 years of age.

The term “activation”, as used herein, refers to a physiological condition upon exposure to a substance, allergen, drug, protein, chemical, or other stimulus, or upon removal of a substance, allergen, drug, protein, chemical or other stimulus.

The terms “active immunization”, “immunization”, and “vaccination”, as used herein, refer to the acquisition of immunologic memory and long-term protection against recurring diseases through antibody production in response to administration of an immunogenic antigen.

The term “cytometry”, as used herein, refers to a process in which physical and/or chemical characteristics of single cells, or by extension, of other biological or nonbiological particles in roughly the same size or stage, are measured. In “flow cytometry”, the measurements are made as the cells or particles pass through the measuring apparatus (flow cytometer) in a fluid stream. A cell sorter, or flow sorter, is a flow cytometer that uses electrical and/or mechanical means to divert and collect cells (or other small particles) with measured characteristis that fall within a user-selected range of values.

Immune system profiling and data output. In order to identify impairment of immune function in an individual, an immune system profile is established from measurements of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines. Following data analysis, the identified immune system profile is transformed into information for graphical display or output to a computer-readable medium, computer or computer network.

DETAILED DESCRIPTION

Embodiments of the present invention provide diagnostic markers of immunosenescence and methods of identifying individuals with impaired immune function based on a combination of such markers obtained from various analyses, primarily from blood, testing immune function including the analysis of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines (‘cytokine response’). Particular combinations of markers can predict with high accuracy whether an individual will respond to active vaccination and become protected against recurring diseases.

Cells of the Immune System

White blood cells or leukocytes are cells of the immune system that defend the human body against infectious disease and foreign materials and are often characterized as granulocytes or agranulocytes, depending on the presence or absence of granules. There are various types of leukocytes, which are all produced in the bone marrow and derived from (multipotent) hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system. Granulocytes encompass neutrophils, basophils, and eosinophils, while agranulocytes include lymphocytes, monocytes and macrophages.

B lymphocytes (“B cells”) and T (thymus) lymphocytes (“T cells”) constitute the two major classes of lymphocytes and play crucial roles in the immune response; hereby provide B cells a ‘humoral’ immune response through secreted antibodies, while T cells provide a cell-mediated immune response through the activation of various cells of the immune systems such as macrophages, natural killer cells, cytotoxic T cells, cytokines etc.

B cells are precursors of antibody-secreting cells and, upon activation, differentiate either into antibody-secreting cells for a primary response via secreted antibodies upon a first exposure to an antigen or into memory B cells which provide a strong antibody response upon a second exposure to that same antigen.

T cells can function as (i) effector cells in cell-mediated responses, as (ii) helper cells in both humoral and cell-mediated immune responses or as (iii) regulatory cells. Typical functions of effector T cells are, for example, the lysis of pathogen-infected cells or the lysis of neoplastic cells, while typical functions of helper T cells are aiding in the production of specific antibodies by B cells; (immune) regulatory T cells, in contrast, are able to suppress immune responses.

The Innate Immune System and Immune Response

Pathogens such as viruses cause an inflammatory reaction in the body through chemokine-mediated recruitment of leukocytes to the site of infection. Neutrophils are attracted first, followed by monocytes, macrophages, natural killer cells, cytokines as well as other innate immune cells. Those innate immune cells then provide critical signals for dendritic cells that help to initiate a T cell-mediated, antigen-dependent or adaptive immune.

Cytokines are peptides, proteins and glycoproteins that are secreted by cells of the immune system and, as signaling molecules, carry signals between cells. Based on their function, cytokines can be classified as lymphokines, interleukins and chemokines. They are often categorized into a) the IL-2 subfamily, b) the interferon (IFN) subfamily and c) the IL-10 subfamily.

T Cell-Mediated, Antigen-Dependent or Adaptive Immune Response

Secondary lymphoid tissues are the focal point of an adaptive immune response, because there naïve T cells are presented with and activated through physical contact with mature dendritic cells that present specific foreign antigen peptide/MHC complexes.

The transition from innate to adaptive phases of the immune response involves antigen uptake by antigen-presenting cells, particularly by dendritic cells. Dendritic cells support clonal expansion and differentiation of activated, antigen-specific T cells by providing proliferative information through foreign antigen peptide/MHC complexes and possibly through costimulatory ligands such as CD80 and CD86, which are ligands for CD28, an important cell-surface receptor on T cells that helps to initiate mitogenic signaling in naïve T cells.

After naïve helper T cells (CD4 T cells) have become activated and begin to divide and differentiate according to signals from dendritic cells and other co-stimulatory ligands, at least three subsets of effector CD4 T cells (T_(H1), T_(H2) and T_(H17)) emerge with specialized homing properties and functions in the adaptive immune response.

Immunosenescence

Defects in both the innate and adaptive immune system have been described and include changes in immune cell subsets abundance and relative frequencies, altered hematopoiesis, impairments in antigen presentation, decreased B cell as well as T cell proliferation, a reduced TCR repertoire and defects in antibody production (Weiskopf et al., 2009). Ultimately these alterations result in a sharp decline in the response to new and persisting antigens and are referred to in the aggregate as immunosenescence. Thus it is not surprising that infectious diseases are one of the major causes of mortality in those over the age of 65 and that protective vaccination of the elderly is more difficult to establish than in younger individuals (Goodwin et al., 2006).

Signal Transducers and Activator of Transcription (STAT) Proteins

The STAT proteins regulate many aspects of cell growth, survival and differentiation. The transcription factors of this family are activated by the Janus Kinase JAK and dysregulation of this pathway is frequently observed in primary tumors and leads to increased angiogenesis, enhanced survival of tumors and immunosuppression.

There are seven STAT proteins, namely STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B and STATE. STAT proteins were originally described as latent cytoplasmic transcription factors that require phosphorylation for nuclear retention. The unphosphorylated STAT protein shuttles between cytosol and the nucleus waiting for its activation signal. Once the activated transcription factors reaches the nucleus it binds to a consensus DNA-recognition motif called gamma activated sites (GAS) in the promotor region of cytokine inducible genes and activates transcription of these genes.

UTILITY OF THE INVENTION

While it is well known that the immune response in older individuals decreases with increasing age, no clear causal link has been established. Due to the complexity of the immune system, only a small fraction of the immune system is conventionally investigated which has made it difficult to draw general conclusions about the phenomena observed to date.

Embodiments of the present invention provide methods to identify individuals, particularly older individuals, who look on the outside healthy, but might already be at an increased risk for infection due to an impairment of their immune system, by comprehensively evaluating, primarily from blood specimen, a multitude of biomarkers obtained from various analyses testing immune function including the analysis of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines (‘cytokine response’). This provides a full picture readout with wide diagnostic applications to individuals of any age who might be at risk of developing an impaired immune function or already experiencing signs of an impaired immune function. Diagnostic application of these biomarkers to individuals of any age and health status followed by an appropriate treatment, if necessary, may reduce the risk of infection as well as morbidity and increase lifespan.

Embodiments of the present invention provide diagnostic markers of immunosenescence and methods of identifying individuals with impaired immune function based on a combination of such markers obtained from various analyses, primarily from blood, testing immune function including the analysis of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines (‘cytokine response’). Particular combinations of markers can predict with high accuracy whether an individual will respond to active vaccination and become protected against recurring diseases

Following active vaccination, older individuals often don't develop a fully functioning adaptive immune response, as would be evidenced by a strong antibody production against an introduced immunogen, and, thus, do not obtain the benefits of long-lasting protection against recurring diseases. It is an advantage of the present invention that particular combinations of markers can predict with a very high accuracy whether an individual will respond appropriately to active vaccination and become protected against recurring diseases.

As illustrated in particular embodiments of the present invention, cell cytokine responses are reduced with age and independent from the stimuli dose (see FIGS. 2 and 3), and correlate with increased cytokine baseline levels (see FIG. 4). Poor cytokine response correlates with other immunosenescence phenotypes (see FIG. 5). Stratification of older adults by cytokine response yields increased resolution to age dependent changes.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. In the following, experimental procedures and examples will be described to illustrate parts of the invention.

EXPERIMENTAL PROCEDURES

The following methods and materials were used in the examples that are described further below.

Sample Collection. Peripheral blood samples were obtained from 29 male and female volunteers aged 18-96 (see Table S8 for demographics) at the Stanford Clinical Trials Research Unit as part of an influenza vaccine study. All volunteers were considered to be currently healthy after an evaluation of their medical history and assessment of their vital signs. Females of childbearing potential were tested for pregnancy by a urine sample. Volunteers had no active systemic or serious concurrent illness, no history of immunodeficiency, nor any known or suspected impairment of immunologic function, including clinically significant liver disease, diabetes mellitus treated with insulin, moderate to severe renal disease, blood pressure >150/95 at screening, chronic hepatitis B or C, recent or current use of immunosuppressive medication. In addition, none of the volunteers were recipients or donors of blood or blood products within the past 6 months and 6 weeks respectively nor showed any signs of febrile illness on day of enrollment and baseline blood draw. Informed consent was obtained from all of the subjects enrolled in this study, and the study protocol was approved by the Stanford University Administrative Panels on Human Subjects in Medical Research (IRBs). In total, 120 ml whole blood (˜40 mL/visit) whole blood was drawn per subject and processed by standard procedures to PBMC and serum, if needed (see below). All analyses described here were performed from samples drawn on the same visit (visit 1) with the exception of cell-subset phenotyping, which were analyzed from blood drawn 21 days after initial visit following verification that cell-subset frequencies do not alter significantly in that time frame.

Whole Blood Gene Expression. Total RNA was extracted from the PAXgene RNA blood (PreAanalytiX GmbH, VWR part # 77776-026, USA) using the QIAcube automation RNA extraction procedure according to the manufacturer's protocol (Qiagene Inc., Valencia, Calif., USA). Amount of total RNA, and A260/A280 and A260/A230 nm ratios were assessed using the NanoDrop 1000 (Thermo Fisher Scientific Inc., Wilmington, Del.). RNA integrity was assessed using the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, Calif.). In each sample the RNA integrity number (RIN) were measured. A two-color gene expression system was used to determine the expressed mRNAs in the given samples. For each sample, 500 ng of total RNA were labeled with Cyanine 3-CTP and 500 ng of Universal Human Reference RNA (Stratagene, Cat Nr: 740000) were labeled with Cyanine 5-CTP. The combined labeled sampled were hybridized onto the Agilent whole human genome microarrays (G4112F, Agilent Technologies, Santa Clara, USA). After hybridization, the mRNA slides were scanned on an Agilent DNA microarray scanner (Agilent Technologies, Santa Clara, USA). Agilent Feature Extraction Software (Version 10.5.1.1) was used to extract the microarray images data. After checking the quality of each subject array, the Feature Extraction files were imported into R Bioconductor and analyzed using the Agi4×44PreProcess package for probe filtering, quantile normalization and replicate probe summarization. We required that probes be detected, above background and the negative controls on the array, unsaturated, and not be detected as a population outlier, or non-uniform outlier with a lower limit of detection of 75. For all subsequent analyses, we included 29,849 array elements whose expression fulfills these criteria. The original microarray data files were entered into the Stanford Microarray Database (http://genome-www5.stanford.edu//), and they can be accessed by choosing “public login” and then selecting experimenter “HIMC” and experiments “Gergana”.

Serum cytokine levels. Serum samples were obtained by centrifugation of clotted blood and stored at −80° C. before cytokine levels determination. 42-plex kits were purchased from Millipore and used according to manufacturer's recommendations with modifications as described below. Briefly, samples were mixed with antibody linked polystyrene beads on 96-well filter plates and incubated at room temperature for 2 hours followed by overnight incubation at 4° C. Plates were then vacuum filtered and washed twice prior to 2-hour incubation with biotinylated detection antibody. Samples were filtered as above, washed twice and resuspended in streptavidin-PE. After incubation for 40 minutes at room temperature, two additional vacuum washes were performed, and the samples resuspended in Reading Buffer. Each sample was measured in duplicate. Plates were read using a Luminex LabMap200 instrument with a lower bound of 100 beads per sample per cytokine. The Luminex LabMap200 outputs the fluorescence intensity of each bead measured for a given cytokine in a sample. For each well, we considered the median fluorescence intensity (MFI) of all beads measured for that cytokine in a well as its abundance and averaged the MFI of the two replicates to obtain the abundance of a cytokine in a sample.

HAI assays. Participants were immunized with one dose of the trivalent inactivated seasonal influenza vaccine (TIV) post baseline blood draw, as described above. Blood samples were collected on day 0 before vaccination, as well as day 7 and day 28 post vaccination. Sera were prepared with the day 0 and day 28 blood samples. The HAI assay was performed using a standard technique (Prevention, 1998); serially diluted 25-μl aliquots of serum samples in PBS were mixed with 25-μl aliquots of virus, corresponding to four HA units, in V-bottom 96-well plates (Nunc, Rochester, N.Y., USA) and incubated for 30 minutes at room temperature. At the end of the incubation, 50 μl of 0.5% chicken (for influenza A/H1N1 and B viruses) or turkey (for influenza A/H3N2 virus) red blood cells was added and incubated for a minimum of 45 minutes before reading for HAI activity. The HAI titer of a given sample was defined as the reciprocal of the last serum dilution with no HA activity. A titer of 2 was assigned to all samples in which the first dilution (1:4) was negative.

PBMC phenotyping. Whole blood samples were subjected to density gradient centrifugation and PBMC were collected for phenotyping and phosphoflow assay (see below). Cells were frozen in DMSO with 10% FBS at −80° C. overnight prior to transferring to liquid nitrogen. For cell subset analysis, cells were thawed, washed twice with warm culture media and stained with the following antibody cocktail: CD3 AmCyan, CD4 Pacific Blue, CD8 APCH7, CD28 APC, CD27 PE, CD45RA PE-Cy5, CD19 Alexa Fluor700, CD56 PE, CD33 PE-Cy7, TCRγδ APC, all reagents from BD Biosciences. Incubation with antibodies was performed for 30 min at 4° C. Cells were washed and resuspended in FACS buffer. Data were collected using DIVA software in an LRSII instrument (BD Biosciences). Data analysis was performed using FlowJo 8.8.6 by gating on live cells, then using double gating for singlet discrimination, followed by cell subset specific gating. The median fluorescent intensity was used in the calculation of percentage of positive cells for a given cell subset.

Phosphorylation of STAT Proteins in Response to Cytokine Stimulation.

Thawed PBMC were rested for 1 hour in warm RPMI media with 10% FBS (culture media) before stimulation. Cells were distributed in 96-deep well blocks and stimulated for 15 min at 37° C. with IFN-γ, IL6, IL7, IL10, IL21 at 50 ng/ml or with 10⁴ U/ml IFN-α. After stimulation, cells were fixed with 1.5% PFA at room temperature for 10 min and washed with an excess of plain PBS. Cells were then span down at 2000 rpm for 5 min at 4° C. and permeabilized with 100% cold methanol for 20 min on ice. Stimuli conditions were barcoded using a 3×3 matrix with Pacific Orange and Alexa Fluor 750 (Invitrogen Corp) at 0.03 and 0.04 ug/ml for low staining and 0.2 and 0.3 ug/ml for high staining, respectively (Krutzik and Nolan, 2006). Incubation with barcoding dyes was performed at 4° C. for 30 minutes. After several washes with FACS buffer (PBS 2% FBS, 0.1% Na Azide) stimulated and barcoded cells were pooled into single tubes and stained for 30 min at 4° C. with an antibody cocktail containing anti pSTAT1 Alexa Fluor 488, pSTAT3 Alexa Fluor 647, pSTAT5 PE, CD3 Pacific Blue, CD4 PerCP-Cy5.5, CD20 PerCP-Cy5.5 and CD33 PE-Cy7 (all from BD Phosflow). After washing, cells were resuspended in FACS buffer and acquisition was performed on an LSRII instrument (BD Biosciences). Data were collected using DIVA software in an LRSII instrument (BD Biosciences). Data analysis was performed using FlowJo 8.8.6. by gating on live cells, then using double gating for singlet discrimination, followed by cell subset specific gating (see Fig. S2 for gating strategy). A drawback of this technology that limits the cell subset resolution is the availability of commercial antibodies that bind to epitopes resistant to methanol fixation. Therefore, we used antibodies to CD3 and CD4 to identify CD4 (CD3⁺CD4⁺) and non-CD4 T cells (CD3⁺CD4⁻); CD20 for B cells and CD33 to identify monocytes. One caveat of this strategy is the contribution of γδ- and NK-T cells to the CD8 signal, because all three subsets are CD3⁺CD4⁻. Gamma-delta and NKT cells constitute only a minority of lymphocytes while the frequency of CD8 T cells is often more than 30% of PBMC. We thus refer to the non-CD4 fraction as CD8⁺ T cells. Phosphorylation of STAT1, 3, and 5 proteins in B cells, CD4/CD8 T cells or monocytes was analyzed by debarcoding on stimuli-specific gating (see Fig. S2). Fold change between stimulated and unstimulated conditions was calculated using the 90th percentile of the pSTAT1, 3, or 5 positive cells. Using the median fluorescent intensity instead of the 90th percentile did not alter the observation of significant age dependent decline in phosphoprotein levels in response to cytokine stimulation.

We analyzed 29 samples at a single cytokine stimuli concentration, performed over the course of 3 days by 2 different subjects. Baseline phosphoprotein abundance in a given cell was measured in 6 replicates, averaged and day normalized by dividing the average measurement on a given day. Fold-change difference due to stimulation was computed as the ratio of the cell, cytokine stimulation, phosphoprotein measure to the raw, un-normalized, cell-phosphoprotein matching baseline that was measured on the same plate. Fold-change values were normalized by the average fold-change difference of a given cell-cytokine stimulation-phosphoprotein measure on a given day. We tested each assay for day dependent differences. No significant differences between days were detected post-day normalization and cytokine responders and non-responders were present in all three days.

For the dose-response assay, we measured three pairs of old and young subjects that we paired on a single 96-deep well plate and stimulated for 15 min at 37° C. The protocol was identical to the one described above, with the exception of the cytokine stimulation doses: for IFN-γ, IL6, IL7, IL10, and IL21 we stimulated cells with 0.1, 1, 10, 50 and 100 ng/ml of cytokine whereas for IFN-α we stimulated with 0.12, 0.25, 0.5 1 and 2×10⁴ U/ml. Baseline phosphorylated STAT levels were measured for each subject per plate in 5 replicates. Sample normalization was performed in the same manner as is described above for all 29 samples. To determine if a fold-change difference exists for a given cell, cytokine, phosphoprotein assay between old and young we used a t-test at the highest dose stimuli concentration and corrected for multiple hypotheses testing (Storey and Tibshirani, 2003). Of the three pairs of old-young samples we tested, one pair was missing a single, but different, measurement for each stimulus. Though the results were fully consistent with those observed in the two other old-young pairs (i.e. the young subject showed increased fold-change for all doses for a large number of assays), we did not include results from this pair in any of the analysis discussed here.

Cytokine levels in cultured monocytes and T cells. PBMC from two young and two older subjects were thawed and washed once with warm RPMI media supplemented with 10% FBS. After 1 hour incubation at 37° C., cells were chilled on ice and washed with cold PBS with 0.5% BSA and 2 mM EDTA. Prior to enrichment cells were incubated for 10 min with FcR blocking reagent (Miltenyi). Monocytes, CD4⁺ and CD8⁺ T cells were negatively selected by magnetic sorting using the Monocyte Isolation Kit 11, CD4 T cell isolation Kit 11 and CD8 T cell Isolation kit (Miltenyi), respectively. More than 85% purity was achieved as evidenced by further staining with cognate antibodies and flow cytometry analysis (not shown). Enriched cell populations were resuspended in serum-free media (AIM V, Invitrogen), plated at 0.5×10⁶/ml and stimulated with IL-6 or IFN-α at 50 ng/ml and 10⁴ U/ml, respectively or left alone. Incubation with cytokines was conducted at 37° C. for 18 hours. Supernatants were analyzed for cytokine expression using the Luminex LabMap200 platform.

Regression analysis for age-associated traits. We used a linear regression model to identify measurements that showed a statistically significant change in expression with age. Our linear regression model accounted for both age and gender differences. Mathematically, our model takes the form:

Y _(ij)=β⁰ _(j) ⁺β_(j) ^(Age)*Age_(i) ⁺β_(j) ^(Gender)*Gender_(i) ⁺ e _(ij)

Where Y_(ij) is the in subject i of measurement of j where j is either a gene expression, cell-subset phenotype, cytokine abundance or baseline phosphoflow measurement. In the case of gene expression and phosphoflow cases Y is in log 2 space. We applied the model to each data measurement. To compute p-values of the beta coefficient of age and gender, we permuted the data measurement with respect to age and gender, 200 times, and then recomputed the regression. For each permutation we tested were the absolute value of the permuted derived betas was greater or equal in size to the absolute value of the true beta coefficients. P-values for each beta were then calculated as the ratio of the number of times the betas from the permuted regressions exceeded the betas the true data regression over the total number of trials. To reduce the effects of outliers on our results, for both the serum cytokine and cytokine response were single subjects (29 and 25 respectively), were outliers, we used a robust regression model with a bi-square weight model. To correct for multiple hypothesis testing, we considered the regression p-values for all measurements of a single data type simultaneously and calculated a q-value (Storey and Tibshirani, 2003) for each. We applied a q-value threshold of 0.15 (unless stated otherwise) and report the p-value of the regression, the age coefficient and q-value. In the case of gene expression we first filtered the data in an independent manner (see below).

Gene subset selection. For gene expression, to restrict the number of multiple hypotheses corrections we were required to make, we considered a selected gene subset of immune and aging related genes for analysis, based on independent prior evidence from unrelated experiments (Table S2).

For immune genes we used ImmPort—the Immunology Database and Analysis Portal (2009) which contains manually curated immune related gene list (Mar. 3^(rd), 2009 version). All entries that did not map to a single ENSEMBL gene ID (mostly those mapping to a specific allele or exon) were discarded. The resultant list includes 3272 genes of which we mapped to the array using Entrez gene IDs. In total 2644 genes had one or more probes on the array for a total of 4708 probes.

We annotated genes as being related to aging and longevity by two different methods. First, we considered any gene that was annotated as aging related in the GenAge database (Build 15, 17 Mar. 2010) (de Magalhaes et al., 2009) as such. GenAge is a manually curated database of genes related to aging. This includes the few genes directly related to aging in humans and the best candidate genes obtained from model organisms. This yielded 243 longevity/aging genes. In addition, we performed a meta-analysis of aging related gene expression datasets to find a robust set of aging related genes. To do so, we identified 58 gene expression datasets (GDS) or gene expression series (GSE), comprising a total of 2152 microarray chips, in NCBI's Gene Expression Omnibus (GEO) (Barrett et al., 2007) which sampled gene expression in ‘normal’ aging across five species: human, rat, mouse, worm, and fly. As an subject dataset or series may combine samples drawn from different experimental conditions, tissue types or populations (such as different mouse strains or genders), these were further divided into a total of 114 comparisons between young and old samples. To create a profile of genes differentially expressed between young and old, we performed two types of meta-analysis. We looked at genes measured in at least ten comparisons, and used the modified t-test (Tusher et al., 2001) and Fisher's exact test, to identify genes significantly differentially expressed between young and old. We also computed a meta effect estimate, a meta fold-change, using a linear model, weighted by the inverse of the variance in expression (Choi et al., 2003). Performing this procedure yielded an additional 261 aging related genes (239 could be mapped on array with an EntrezID).

Network construction and spCCA. We identified as set of immune system modules from peripheral blood which best correlated with cell-subset specific cytokine responses in five steps: sample outlier filtering, supervised functional classification, within data type correlation and spCCA to identify co-regulated clusters.

First, for each of the 5 different data types (gene expression, cell subset, serum cytokines, cytokine stimulation response and baseline phosphoprotein levels), we filtered outlier samples that may have strong effects on correlation analysis by computing for each datatype, the overall sample correlation. Samples whose distance from all other samples was markedly different were removed from this analysis. This procedure identified two outlier samples, one sample (29) from the serum cytokine dataset and one sample (25) for cytokine response assays. Next, for specific data-types we classified nodes by function and/or co-expression. In particular cytokine responses were classified by type (baseline, response or baseline and response), cytokines by functionality. For phosphoprotein baseline measurements we clustered the data from the different STAT molecules within a cell together. Cell subsets were maintained as unique nodes at the cellular level. To cluster by co-expression we used the R library WGCNA (Langfelder and Horvath, 2008) which dynamically dissect clusters of strong correlations by exponentiation of the correlation matrix by a positive value determined empirically for each dataset by a fit of cluster connectivity to a scale free topology. We set the minimal cluster size for all datasets to 1, with the exception of gene expression for which minimal cluster size was set to 10. The outcome of applying this procedure for each dataset was to group highly correlated measurements in each data type together. This procedure yielded: (1) four cytokine response nodes, one for each cell subset, (2) three phosphoprotein nodes containing all age-associated baseline differences by cell type, (3) six nodes representing cell-subset frequencies, (4) five serum cytokine nodes, and (5) six gene expression nodes and two singletons containing all 279 age-associated genes (see Table S5 for which measurements were captured in each node).

For the purpose of identifying those measurements that are correlated with the cytokine response phenotype, we split the above described immune measurements into two matrices, the first consisting solely of subjects' cell-type average cytokine response and the second of all other factors/clusters and then applied spCCA (Witten et al., 2009). To set the penalty tuning parameters we performed sparse canonical correlation analysis on the real data set compared the magnitude of the first maximally correlated association to that observed in 1000 permutations of the data over a range of penalty parameters equally set for each data type. We observed similarly high z-scores (above 3) across the entire range of tested parameters. Penalties of 0.5 and 0.7 were chosen for the two matrices respectively as they showed a good z-score, strong correlations between measurements (r=0.89, r_(permuted)=0.59, p-value <0.001) and a reasonable number of non-zero weights for interpretation. Importantly, though a cytokine response may consist of a weighted average of each of the four cell types, setting the penalty to 0.5 yielded a single non-zero weight for cytokine response, corresponding to a single cell-type, for each recursive iteration of the algorithm. A more permissive penalty (0.7) yielded multiple non-zero cytokine response but for only a minor gain in increased correlation. Thus, the linear combination of immune measurement we report is based on a 0.5 penalty and to a first approximation is orthogonal and maximally correlated with a single cell-type in which the cytokine response deficiency is observed. To enable comparison of the four weighted modules, weights were normalized by the maximum weight within a given linear combination and multiplied by the correlation of that maximal correlation observed between that module and the single unit weight of the cytokine response. We note that despite normalization of all the data, the magnitude of baseline phosphoprotein and cell-type frequency association with cytokine responses may be inflated by their measurement on the same technological platform.

Classification and Comparison of Cytokine Response Profiles. We introduced two modifications to the cytokine response classification protocol for the longitudinal analysis the years subsequent to year 1: First, as the range of the data in the assay was reduced in the subsequent years (likely due to antibody batch effects), we used a standard deviation threshold of one (instead of two) from the responses of the young group returning that year, to determine an subject's cellular response state. Second, if a response of a young subject was in itself an outlier, the mean and standard deviation of the young group was recomputed leaving that result out, effectively maintaining the scoring system as relative to good health. This latter procedure was not required in the first year, as the cell-specific distribution of young subjects was very tight there were no outliers.

To evaluate how stable the cytokine response phenotype was over the course of the three years, we created a model for the likelihood of remaining in the same classification or moving toward the non-responder category and compared this to the null model where the classification for any given year is random (i.e. equal probability of being classified into one of the three categories each year).

In the direct comparison of CR to CNR, as the number of samples did not permit direct consideration of gender and age in the comparison, we estimated their effect by single variable comparisons of gender and old-age differences in the data.

Tests of significance for determining immune response deficiency type. We used the dose-response data to distinguish between baseline and response causes for the lower fold-change levels we observed in the older subjects. To do so we devised a decision tree consisting of 6 consecutive tests, the application of which on a given cell, cytokine stimulation, phosphoprotein assay should implicate the mechanism inhibiting the full fold-change response:

-   -   (1) Use a one-tailed t-test to test whether the baseline         phosphoprotein levels in the older subjects are significantly         higher than that of the young (uses the complete dataset).     -   (2) Use a one-tailed t-test to test whether a significant         fold-change difference is observed between the two older         subjects and the two younger at the highest dose level.     -   (3) Use an f-test on computed ratio of fold-change between the         lowest and highest stimulation doses to test if dose-response         curve of the older subjects show a significant incline.     -   (4) Use an f-test to test if the dose-response of the younger         subjects (ratio of fold-change between the lowest and highest         stimulation doses) is significantly greater than that of the         elderly.     -   (5) Use a two-tailed t-test to ask if the MFI at the highest         stimulation dose is equal between the elderly and young         subjects.         Tests (1) and (2) are used to identify if baseline         phosphoprotein level differences, fold-change or both exist.         Test (3) is used to identify if a given assay is in saturation         for all doses, whereas (4) identifies if saturation is only         observed in the older subject group or alternatively if no         saturation exists, whether the younger subjects are more         sensitive in their response for an increased dose. In the case         test (4) indicates saturation of response in the older subjects,         test (5) asks whether both the older subjects and the young         reached saturation and if so, was it at the same ceiling (total         available protein for phosphorylation).

Examples

The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention; they are not intended to limit the scope of what the inventors regard as their invention. Unless indicated otherwise, part are parts by weight, molecular weight is average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric.

Example 1 Age-Dependent Differences are Detectable from the Cellular to the Molecular Level

Age-dependent differences were detectable from the cellular to the molecular level. To identify age-associated differences, multiple regression analysis was performed a on all samples according to age and gender. For multiple hypotheses correction, a false discovery rate was chosen that maximized the number of true positives while still being amenable for follow-up analyses. The false discovery rate is denoted as q-value and was set to q≦0.15 unless otherwise noted; see Figure S3 and Experimental Procedures.

In white blood cells a decrease in CD8⁺ naïve cells was detected with age, but no other age-associated changes in cell subset frequency. A high variance in frequency was noted between individuals that was particularly prominent in the elderly group (>73 years old) and that affected the regression analysis. However, at a q≦0.25, 8 of the 15 cell subsets surveyed showed age-associated changes in frequency (see Table S2). These included an increase in the frequency of monocytes, and an increase in CD8⁺ and CD4⁺ cells lacking CD28 expression, which is a critical molecule for robust T cell activation in both CD8⁺ and CD4⁺ T cells. In addition, increases in the frequency of NKT cells were noted and in both CD8⁺ and CD4⁺“memory” T cells, i.e., the cells that respond to previously encountered antigens.

Table S2 summarizes twelve serum proteins whose serum levels were changed as a function of age. These included the chemokines IP-10 and Eotaxin, both of which increased sharply with age as previously reported (Shurin et al., 2007), as did IL-12, which is known to regulate IP-10 production. The only pro-inflammatory cytokine that was found to increase with age was TNF-α. Both Th1 (IFN-γ and IFN-α2) and Th2 (IL-4, 5, 7) related cytokines decreased with age, as did the macrophage activation cytokines MRC-3 and TGF-α. With respect to the ability of white blood cells of these individuals to functionally respond to signaling cues from cytokines, of the 12 baseline and 72 response assays that were conducted (4 cell subsets, stimulated by 6 cytokines and measuring phosphorylation level of STAT-1, -3, and -5), an age-associated difference in 8 baseline and 39 response measurements was detected, 33 of which showed a 2-fold or greater response to stimulation in at least one person (see FIG. 1A-C, Figure S3A-B).

The gene expression analysis in these studies was limited to those genes which had previously been independently associated with either immunological or longevity phenotypes. Based on curated databases of immunology (2009) and aging (de Magalhaes et al., 2009) 2713 immune-related genes and 239 aging-related genes were measured on human genome microarrays (Agilent 4×44 whole human genome microarrays). A cross-species meta-analysis of 114 aging-related gene expression experiments identified an additional 40 genes (see Table S3 and S4). In total, these comprised 2863 genes that corresponded to 4364 unique probes on the array. Testing this set of probes for age-associated differences yielded 294 probes (q≦0.15, Figure S3E), which corresponded to 279 unique immune and aging-related genes that were found up- or down-regulated with age (see Table S2).

Example 2 The Cytokine Responses of Older Adults are Systemically Reduced, Independent of Concentration

Cytokine response assays that assess the phosphorylation state of intracellular signaling proteins have been shown to be predictive of disease outcome in several cases (22; 27). On average older individuals exhibited lower phosphorylation states in response to stimulation than the young (FIGS. 1A and 1B). To address the possibility that low responses to cytokines might be due to low sensitivity of cells from older individuals, dose-response experiments were carried out and increasing concentrations of all 6 cytokines were assayed in all 4 cell subsets in 2 young and 2 old poor cytokine responders. Differences between old and young were consistently observed in the majority of assays (FIG. 1D, Figure S4), even at the highest, saturating doses (Figure S5). 30 age-associated differences were identified at the highest cytokine concentrations; of those, 20 showed a 2-fold or higher change and a significant reduction in the responses of older individuals versus the younger cohort (FIG. 1D, Figure S4). Thus, in comparison to young individuals, older individuals were not able to mount an equally strong response to cytokine stimulation, even at saturating levels. Furthermore, individuals who were deficient in one cytokine response were, for the most part, deficient in others as well. This correlation was also true across cell-types. For example, those individuals who were deficient in their CD4⁺ T cell responses also tended to be deficient in their CD8⁺ T cell responses and in many cases in either or both monocytes and B-cells, suggesting a systemic condition (see FIG. 1E). Taken together, multiple impairments to respond to cytokine signals occurred with age, independent of the stimuli concentration.

Example 3 Cytokine Response Deficiencies and Immunosenescence Markers Co-Occur in the Single Individuals

In further studies, a potential relationship was investigated between the cytokine response phenotype and other immune measures such as cell subsets and cytokines. This revealed a high concordance of the cytokine response deficiency with hallmarks of immunosenescence alterations in cell subsets (see FIG. 2A, top), such as the drop in CD8⁺ and CD4⁺ naïve cell frequencies (R²=0.54, p<10⁻⁶ and R²=0.54, p<10⁻⁶ respectively) (Fagnoni et al., 2000), the increase in occurrence of CD8⁺CD28⁻ cells (R²=0.54, p<10⁻⁶) (Effros et al., 2005; Fagnoni et al., 1996) and the decline in B-cell frequency (R²=0.23, p<0.01).

Cytokine responses in serum proteins showed significant association with log transformed intensity measurements of macrophage chemokine MCP-1 (R²=0.23, p<0.01) and more mildly with the innate immunity chemokine IP-10 (R²=0.18, p<0.07) (see FIG. 2A, bottom). However, pro-inflammatory cytokines showed no significant association with reduced cytokine responses. Aside from TNF-α, no increase in pro-inflammatory cytokines in serum was detected. In particular, no significant age or cytokine response association was observed for IL-6, whose increase has been associated with aging in many other studies (Franceschi et al., 2000; Shaw et al., 2010; Wikby et al., 2006), and has most recently been linked with mortality (Wassel et al., 2010). For a direct analysis of cytokine levels from sorted cells, monocytes, CD4⁺ and CD8⁺ T cells from PBMC of two young and two older individuals were isolated and cultured, and then the secreted cytokine levels of these cells were profiled across 50 different cytokines after 18 hours of incubation at 37° C. These assays showed a dramatically increased abundance of pro-inflammatory cytokines (IL-6, IL-1b, TNFα) and chemokines (CXCL1, CXCL5) in the monocytes of the older individuals (see FIG. 2B). No other significant differences in cytokine abundance were detected either in monocytes or in the CD4⁺ or CD8⁺ T-cells. Taken together, these associations suggested that a subset of older individuals exhibited immune system impairments that were concomitant at multiple levels, and to which the systemic reduction in cytokine response was closely linked.

Sparse canonical correlation analysis (spCCA) (Witten et al., 2009), an unsupervised statistical technique, was used to identify linear combinations of weighted factors, that showed maximal correlation with cytokine response. For simplification, highly co-varying factors internal to a single type of measurement were first clustered, including the cytokine responses themselves by cell subsets. spCCA identified four distinct and significant maximally correlated sets of factors, one for each of the four cell subsets in which cytokine response deficiencies had been observed (see FIG. 2C and Table S6). These multi-factor combinations (‘modules’) showed considerably higher correlation with cytokine responses than the correlation that were observed with single known immunosenescence markers. The specific combination of an increase in B-cell baseline phosphoproteins, a decline in CD8⁺ naïve cell frequency and 14 other factors formed a module which correlated with B-cell cytokine response with an r=0.89 at a significance of p<0.0001. (r=0.87, 0.87, 0.74 for CD4+, CD8+ and monocytes respectively). The modules correlating with a cytokine response deficiency of a given cell subset often included molecular measurements from cell subsets other than their own and at higher weights, indicating inter-cellular dependencies of these deficiencies.

Example 4 Cytokine Responses Define Distinct Age-Related Subgroups that are Longitudinally Stable; Definition of Cytokine Responders Versus Cytokine Non-Responders

For assessing the extent of variation in the various analyses, a scoring system for cytokine deficiency was defined by first calculating for every individual the sum of age-associated cytokine responses in each cell subset, and then comparing to see if it was markedly different from that observed in the young group for that cell subset (two standard deviations from the mean of the young).

The scoring system was defined as a relative scoring system with respect to those generally considered healthy, and reflected the extent of both intra- and inter-cellular effects of cytokine response deficiencies on an individual's immune system.

Under this scoring system, none of the young individuals showed any cytokine response impairments, whereas multiple impairments were observed in older individuals. Furthermore, among older individuals we observed a high amount of variation in the cytokine response score, suggesting the possibility of distinct phenotypes. Therefore, older individuals were defined as cytokine responders (CR), if the sum of their responses in each of the cell subsets was within two standard deviations of the average response in the young individuals in at least three of the four tested cell subsets. Accordingly, older individuals were defined as cytokine non-responders (CNR), if their sum of age-associated responses was below two standard deviations of the average response in the young individuals in at least three of the four tested cell subsets (see Figure S6 and Experimental Procedures). Under these criteria, six older individuals were identified as CR and six as CNR. The remaining seven older individuals we designated as ‘Intermediate’, as they did not meet either of these extreme criteria, but rather showed generally milder reductions in response to cytokine stimulation than observed in CNR and in only one or two of the four tested cell subsets (see FIG. 3A).

To determine the stability of the cytokine response phenotype, a subset of patients (n=21) was examined who had returned to participate in a subsequent three year-long longitudinal study. A similar scoring system was used to classify the response, with minor modifications (see Experimental Procedures). The analysis of each of the three years of the study showed conservation of the cytokine response phenotype both at the cell-type level and the class (CR, CNR or Intermediate) (see FIG. 3B, p=0.019 by permutation). This was particularly notable amongst older individuals, with individuals generally maintaining either the same state or progressing towards the non-responder category.

Furthermore, most shifts in cytokine response state were gradual, meaning that CR did not shift to a CNR state in directly subsequent years or vice versa, but rather passed through the intermediate state. The results from the longitudinal data strongly suggested that fluctuations are not random, but rather a true biological phenomenon whose phenotype in individuals is likely to remain invariant or worsen over time.

Example 5 Cytokine Responders and Cytokine Non-Responders Have Distinctly Different Immune System Profiles

The CR and CNR profiles form two distinct and stable extremes of an important immune phenotype. Further studies were carried out to investigate whether stratification by cytokine response and direct comparison between groups would uncover further significant differences. The participating individuals in this study were vaccinated with a seasonal, inactivated influenza vaccine containing three different strains of influenza. Their antibody titers against all three strains were tested before and approximately 3 weeks after vaccination using a standard hemagglutinin inhibition assay (HAI). It is generally accepted that, at the population level, a pre-vaccination antibody titer of 1:30 to 1:40 represents a 50% probability of protection against Influenza infection (Hobson et al., 1972; Potter and Oxford, 1979; (Coudeville et al., 2010).

Here, the young and the CR group showed similar pre-vaccination antibody titer levels, which were significantly more robust than those of CNR when considered simultaneously across all strains (see FIG. 4A, p=0.0005 and p=0.06 respectively, by Fisher's exact test performed on p-values obtained from permuted data). Response to vaccination, as measured by antibody titers post-vaccination, were similar in CR and CNR (see Figure S7), suggesting that the CNR group had remained responsive to the vaccination and would, therefore, particularly benefit from vaccination.

In addition, the individuals in this study were also tracked with respect to their medical history and concomitant medication. A third of CR individuals reported previous cardiovascular related surgery or hypertension versus two thirds of CNR. While there was a great variation in the medications that the individuals took, the CNR group took significantly more medications than the CR group (p<0.06), which was likely due to the higher incidence of cardiovascular issues in the CNR group. Yet no single mechanism-of-action drug class distinguished CNR from CR (see Table S8), suggesting that the differences between the two groups were not the result of a simple drug effect, but rather a surrogate of their medical condition.

In further analyses, all genomic, molecular, and cellular measurements that had been obtained in the course of the described studies were investigated for specific differences between the CR and CNR groups. A uniform threshold across all measurement modalities of q≦0.1 (see Figure S8) identified 1565 measurements that were different between CR and CNR (ANOVA, see Table S7, similar results were obtained by a permutation test). The CNR group showed a significant decrease in most (48/72) of the cytokine stimulation response assays. In agreement with our current knowledge of low phosphoprotein baseline levels being the cause for any cytokine response defects, elevated baseline phosphorylation was detected in CNR individuals for STAT1, 3 and 5 proteins in B- and CD4⁺ T-cells, as well as for STAT1 in monocytes. 13 out of 15 measured cell-subsets had detectable differences in frequency between CR and CNR (see Table S7), including significantly lower levels of B-cells, CD8⁺ and CD4⁺ naïve T-cells (p≦0.01), and CD8⁺CD28⁻ T-cells (p<10⁶), all known markers of immunosenescence. No serum proteins were detected as differentially expressed between the two groups.

The increase in CD8⁺CD28⁻ T cells and the evidence of an inflammatory state was found to be consistent with the previously described “Immune Risk Profile” for immunosenescence (Wikby et al., 2006). This profile was previously estimated to be present in 16% of older individuals 60-94 years of age (Wikby et al., 2008). Furthermore, it had been reported that individuals with such a profile showed increased morbidity and mortality (Strindhall et al., 2007). An inverted CD4/CD8 cell subset ratio (below 1), is characteristic of such an immune risk profile (Strindhall et al., 2007; Wikby et al., 2008). Therefore, the relationship of the CD4/CD8 ratio to age and cytokine response was also analyzed in the present studies (see Figure S9). Only three individuals (one young, one a CNR and the other an intermediate) had a CD4/CD8 ratio below 1. Furthermore, the CD4/CD8 ratio was highly variable, not only in the present studies, but also in much larger cohorts, investigated by other groups (Lifson et al., 1985), where the CD4/CD8 ratio has been reported to generally rise as opposed to decrease with age. In the present studies, most young individuals showed much lower CD4/CD8 ratios similar to that of CNR, whereas CR showed elevated CD4/CD8 ratio levels.

1493 mRNAs were detected as differentially expressed between CR and CNR (see Table S7). Further studies detected 151 longevity-associated genes that were differentially expressed between the CR and CNR individuals (Table S7). These included genes in multiple pathways associated with lifespan, such as redox (e.g. SOD1, p<10⁴), DNA surveillance (e.g. SIRT6, p<0.02), nutrient sensing (insulin-like growth factor 1 receptor p<10⁻⁵), apoptosis (e.g. the forkhead transcription factor FOXO/DAF-16 family members FOXO1, FOXO3 and FOXL2 p<10⁴) and cellular proliferation (e.g. cMyc, MDM2, p<0.04).

Within the context of immune cell function, these genes may either be in conflict or parallel their role in lifespan extension (match directionality). Genes of the growth hormone signaling pathway were upregulated in CR individuals, while genes of the redox response pathway were downregulated in CRR individuals, according to their expected directionality in longevity. In contrast, genes in the insulin response pathway and cellular proliferation genes were up-regulated in CR over CNR, and appeared to be opposing longevity, but in tune with a functionally active immune system (Jones and Thompson, 2007), a possible necessity for long life in a non-sterile environment. The three cytokine response phenotypes (CR, intermediate or CNR), that had been identified in the older individuals, were almost entirely reflected at the gene expression level when clustering older individuals by the set of longevity associated genes, as shown in FIG. 4B. These results suggest that cytokine response stratification can identify older individuals with distinctly different immune system profiles and differing influenza protection phenotype.

Example 6 Classification of Age-Associated Differences by Cytokine Response

A major conundrum in the study of aging is to ascertain whether a detectable age-associated change describes a process of deterioration or one that is protective. In the present studies, genes and immune traits were investigated that were different between either the CNR and the young or the CR and the young (q≦0.15, Fig. S10), but that were not different in the same direction in the reciprocal group comparison (q≦0.2). A third comparison targeted age-associated differences that were shared between the CR and CNR (q≦0.2). In total, this procedure classified 215, 1,901 and 378 measurements as CNR specific, CR specific or shared between the CR and the CNR (see FIG. 5A for summary statistics, Figure S11 and Tables S9-S11).

The majority of immunosenescence markers identified in the present studies were specific to CNR, whereas the profile of CR was closer to that of the young (see FIG. 5B). For example, the frequency of B-cells in the blood had previously been reported to decline with age (Ademokun et al., 2010), but comparing the two subgroups each directly to the young revealed that B-cell frequency decline was indeed correlated with aging, but only in the CNR group (p<0.004). Similarly, a NKT cell increase had been reported in aging (Shaw et al., 2010) but this was again only observed in CNR.

For both B-cell and NKT cell frequencies, CR showed the reciprocal phenotype (high B-cell, low NKT cell frequency) when compared to the young. For other previously identified age associated changes, such as CD8 naïve cell frequency or serum Eotaxin abundance, both groups showed consistent differences compared to the young, though the change in magnitude was not significant in CR.

CNR specific changes included large shifts in cell subset proportions, additional cytokine responses that were impaired and increased baseline elevations for all cells but CD8+ T-cells (see Figure S11). Only few (138) genes were detected as differentially expressed with age and specific to CNR. In contrast, for CR-specific changes, numerous genes (1896 genes) were differentially expressed with other immune phenotypic characteristics being similar to those observed in the young. In general, CR and CNR shared very few differences with respect to the young, and of them few were previously associated with aging.

Elevated baseline levels and decreased cytokine responses in CD8⁺ cells were common to both CR and CNR, though milder in CR. In addition, at higher q-value thresholds (q≦0.18 for CNR vs. young and q≦0.3 for CR vs. young) most measured serum cytokines significantly differed in their abundance in comparison to the young, likely reflecting increased inflammation (Franceschi et al., 2000) and large changes in cell subset composition. These results indicated that there is likely no common profile of immune aging. Instead it appeared that the immune system of CR and CNR were aging on different trajectories yielding a distinct immune system profile.

Example 7 Reduced Responses to Cytokine Stimulation are Primarily Due to Increased Basal Levels of Phosphorylated STAT Proteins and Alterations in Response Potential in the IL-6 and IFN-A Pathways

The present studies confirm reports that cells of older individuals, particularly of CNRs, experience in vivo an increased inflammatory environment when compared to young individuals (Franceschi et al., 2000). The reduced response to cytokine stimulation, as observed in CNRs, may either be successful adaption to such an environment or resistance to signaling cues. Considering that the changes measured in the cytokine stimulation assays are relative to a baseline pre-stimulation measurement, there are four possible models that could explain the observed unresponsive cells phenotype: (1) an increased exposure to cytokines is leading to successful adaptation and a requirement of higher cytokine concentration, (2) a reaction defect, in which the signaling machinery of cells in the older subjects is leading to a lower response in the older subjects, (3) a baseline defect, in which elevation in baseline pSTAT levels leaves no protein left to phosphorylate and thus decreased pSTAT fold-change, or (4) a combination of both the baseline and reaction pathway defects (see FIG. 6A).

As the observed defected cytokine response occurred systematically in different cells, cytokines, and pSTATs, each may be attributed to a separate mechanism. In the single dose assay that was performed with all 29 individuals, the concentration, baseline and response differences could not be decoupled to identify the factors contributing to the observed reduced fold-change response. Indeed, plotting each subject's cytokine response fold-change levels to the measured baseline levels of the phosphoprotein revealed an inverse correlation with the fold-change response across many of the assays (see FIG. 6B and Figure S12), showing the importance of increased baseline pSTAT levels.

Discriminating between the above mentioned four models could be possible by reanalyzing the dose-response assay conducted in the present studies, which included two young and two old CNR subjects, measured at each of the 72 stimulation assays and baseline for five different doses per cytokine (see Experimental Procedures). A series of tests was applied to the dose-response assay data, using information from the single dose assay whenever possible. In the successful adaptation model (Model 1), the older subjects would be expected to respond similarly to the young at a higher dose of cytokines (see FIG. 6A, top left panel). Conversely, if the relative reduction in response to cytokine stimulation compared to that of the young remained, irrespective of the dose of cytokines, then the reduced response would result from signaling resistance (Models 2-4). These four models can be distinguished for each cell subset, cytokine, and pSTAT assay combination by following a decision tree (see FIG. 6C for a sketch and Figure S13 for a full decision tree, also see Experimental Procedures).

The application of the decision tree (from Figure S13) showed not a single case of adaptation. Of the 30 combinations of cell, cytokine, and pSTATs in which young and older subjects show differing responses, only the monocyte stimulations could be classified solely as a reaction defect, which suggested that these cell subsets—shown to be the main source of pro-inflammatory cytokines in CNR—might not be influenced in an autocrine manner insofar as showing elevated pSTAT baseline levels. All other cytokine responses showed a significant elevation in the older subjects' baseline pSTAT levels, with 11 due solely to a baseline elevation, and 14 to a combined baseline-reaction effect (Table S12). The combined baseline and response factor differences were predominantly seen in T cells stimulated by IL-6 or CD8⁺ T cells stimulated by IFN-α, whereas elevated baseline levels of pSTATs accounted for all of the observed differences in IL-10 stimulation in CD4⁺, CD8⁺ and B-cell and to a lesser extent those involving IL-21, IL-7 and IFN-α response differences. Thus, the reduced cytokine responses in older individuals can predominantly be attributed to an elevation of baseline phosphorylation levels of STAT proteins in cells and to an altered response potential in the IL-6 and IFN-α pathways.

Although the foregoing invention and its embodiments have been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. Accordingly, the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope.

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APPENDICES

Appendix A—Table S1

Appendix B—Table S2

Appendix C—Table S3

Appendix D—Table S4

Appendix E—Table S5

Appendix F—Table S6

Appendix G—Table S7

Appendix H—Table S8

Appendix I—Table S9

Appendix J—Table S10

Appendix K—Table S11

Appendix L—Table S12

APPENDIX A

TABLE S1 Demographics Table Enrollment Enrollment Enrollment Category Category Category 18-30 years 60-79 years 80-100 years Number enrolled n = 10 n = 11 n = 8 Gender Female 6 6 4 Male 4 5 4 Age Mean (yrs) 24.42 64.21 85.44 Range (yrs) 21-28 60-74 83-96 Ethnicity Hispanic 3 0 0 Non-Hispanic 7 11 8 Race White or Caucasian 5 11 8 Asian 3 0 0 American Indian/ 0 0 0 Alaska Native Pacific Islander 0 0 0 Black/African Amer 0 0 0 More than one race 1 0 0 (More than 1: Cauc/Asian) Other Race 1 0 0 (Other: not specified) Declined to answer 0 0 0 Note: Demographics table displays enrollment as per original IRB. The enrollment category 60-79 yo included 10 subeject betweeen the ages of 60-65 and one individual that was 74 yo. That individual was visualized as within the oldest age group and considered within that group for all pertinent analyses

APPENDIX B

TABLE S2 Significant age-associated measurement from Cell subset - Mean Mean Name Yng Old p Age q Age p Gender q Gender CD8 NAIVE 71.62 48.33 0.005 0.15 0.14 0.42 CD8 TERM 14.68 28.47 0.065 0.175 0.155 0.4 DIFF EFFECTOR MEMORY MONOCYTES 26.91 33.86 0.07 0.175 0.28 0.45 CD8+CD28− 22.98 43.55 0.065 0.175 0.065 0.35 CD4 TERM 0.65 3.41 0.02 0.1875 0.265 0.45 DIFF EFFECTOR MEMORY CD8 CENTRAL 11.78 18.48 0.095 0.2143 0.425 0.53571 MEMORY NK T CELLS 5.76 9.89 0.12 0.225 0.275 0.45 CD4+CD28− 1.63 4.02 0.045 0.25 0.3 0.45 Serum cytokines - Mean Mean Name Yng Old pAge qAge p Gender q Gender EOTAXIN 238 427.58 0.01 0.0788 0.715 0.93333 IFN-G 137.98 49.86 0.01 0.0788 0.12 0.45818 IL-7 82.02 98.27 0.01 0.0788 0.12 0.45818 MCP-3 121.81 162.92 0.01 0.0788 0.675 0.89091 IL-12-P70 28.13 19.08 0.005 0.105 0.3 0.63 IL-17 150.77 28.96 0.005 0.105 0.355 0.73044 IL-4 55.63 98.19 0.005 0.105 0.455 0.72414 TGF-a 40.08 60.01 0.005 0.105 0.14 0.42 IP10 462.3 1052.06 0.025 0.126 0.465 0.72414 TNF-A 26.09 42.98 0.025 0.126 0.02 0.35 IFNA2 51.86 91.98 0.035 0.14 0.995 1 IL-5 12.76 18.36 0.035 0.14 0.015 0.42 Cytokine responses Yng Old pAge qAge pGender qGender cd20_IL7_STAT3 0.99 1.04 0 0.0277 0.15 1.54286 cd4_IFNa_STAT5 1.16 0.87 0 0.0277 0.295 1.66154 cd4_IL6_STAT5 1.26 0.71 0 0.0277 0.83 0.95294 cd4_IL21_STAT1 1.15 0.83 0 0.0277 0.515 1.00465 cd4_IL21_STAT5 1.14 0.92 0 0.0277 0.74 0.9 cd8_IFNa_STAT1 1.35 0.66 0 0.0277 0.64 0.91636 cd8_IFNa_STAT3 1.15 0.79 0 0.0277 0.435 1.09091 cd8_IFNa_STAT5 1.2 0.78 0 0.0277 0.415 1.09091 cd8_IL6_STAT1 1.57 0.58 0 0.0277 0.265 1.66154 cd8_IL6_STAT5 1.45 0.8 0 0.0277 0.42 1.09091 cd8_IL21_STAT1 1.28 0.79 0 0.0277 0.74 0.9 mono_IFNa_STAT1 1.13 0.87 0 0.0277 0.37 1.44 mono_IL7_STAT5 1.09 0.95 0 0.0277 0.48 1.09091 cd4_IL7_STAT5 1.08 1 0.005 0.036 0.72 0.9 cd8_IFNg_STAT1 1.37 0.9 0.005 0.036 0.13 1.56 cd8_IL7_STAT1 1.13 0.94 0.005 0.036 0.43 1.09091 cd8_IL10_STAT1 1.19 0.91 0.005 0.036 0.61 0.91636 cd8_IL21_STAT5 1.07 0.89 0.005 0.036 0.545 1.00465 mono_IFNa_STAT3 1.08 0.78 0.005 0.036 0.945 1 mono_IFNa_STAT5 1.04 0.81 0.005 0.036 0.7 0.91636 cd4_IFNa_STAT1 1.19 0.78 0.01 0.045 0.785 0.9 cd4_IFNa_STAT3 1.06 0.64 0.01 0.045 0.515 1.00465 cd4_IL6_STAT1 1.27 0.77 0.01 0.045 0.74 0.9 mono_IFNg_STAT3 1.07 0.89 0.01 0.045 0.8 0.9 cd20_IFNa_STAT3 1.04 0.92 0.015 0.0533 0.53 1.00465 cd8_IL6_STAT3 1.15 0.67 0.015 0.0533 0.275 1.66154 mono_IL6_STAT3 1.09 0.7 0.015 0.0533 0.97 1 cd4_IL6_STAT3 1.08 0.66 0.02 0.0621 0.595 1.00465 cd4_IL21_STAT3 1.07 0.69 0.02 0.0621 0.485 1.09091 cd8_IL7_STAT3 1.01 0.93 0.025 0.072 0.1 1.44 cd4_IL10_STAT1 1.05 0.81 0.03 0.0813 0.615 0.91636 cd20_IFNa_STAT1 1.01 0.79 0.035 0.0873 0.48 1.09091 cd4_IL10_STAT3 1.03 0.69 0.035 0.0873 0.65 0.91636 cd4_IL7_STAT3 1 0.9 0.045 0.1059 0.435 1.09091 cd20_IFNg_STAT3 0.99 1.03 0.05 0.12 0.02 1.8 mono_IL6_STAT1 1.06 1 0.05 0.12 0.555 1.00465 cd4_IFNg_STAT1 1.05 0.89 0.06 0.1362 0.325 1.44 cd20_IFNa_STAT5 1.04 0.92 0.075 0.1477 0.82 0.95294 mono_IFNg_STAT5 1.05 0.88 0.08 0.1477 0.81 0.95294 Phophoprotein baseline Yng Old pAge qAge pGender qGender cd20_Unstimulated_STAT1 0.96 1.69 0 0.03 0.94 1 cd8_Unstimulated_STAT1 0.73 1.18 0 0.03 0.24 0.45 cd4_Unstimulated_STAT1 0.87 1.55 0.005 0.04 0.17 0.432 cd20_Unstimulated_STAT3 0.98 1.03 0.055 0.1029 0.075 0.32 cd8_Unstimulated_STAT5 0.97 1.05 0.055 0.1029 0.095 0.3 cd4_Unstimulated_STAT3 0.94 2.37 0.03 0.105 0.27 0.45 cd4_Unstimulated_STAT5 0.97 1.02 0.04 0.108 0.055 0.36 cd8_Unstimulated_STAT3 0.9 1.07 0.08 0.12 0.03 0.42 Gene Entrez Probe is Expression Id Id Yng Old p Age q Age p Gender q Gender Aging LRP10 26020 A_24_P

7.16 7.31 0 0.1254 0.765 0.91489 0 HLA-DRB5 3127 A_23_P

9.05 9.7 0 0.1254 0.345 0.67843 0 PSTPIP1 9051 A_23_P

7.92 8.28 0 0.1254 0.52 0.8114 0 GRB2 2885 A_24_P

10.69 10.81 0 0.1254 0 0.24244 1 HLA-J 3137 A_24_P

13.73 14.28 0 0.1254 0.735 0.91489 0 PURB 5814 A_24_P

11.3 11.41 0 0.1254 0.54 0.8114 0 CFD 1675 A_23_P

11.32 11.56 0 0.1254 0.05 0.33742 0 LSP1 4046 A_23_P

10.89 11.18 0 0.1254 0.13 0.40962 0 NKX2-3 159296 A_24_P

7.13 7.42 0 0.1254 0.715 0.91489 0 MCL1 4170 A_24_P

13.97 14.2 0 0.1254 0.655 0.8644 0 FCGR2A 2212 A_23_P

8.04 8.16 0 0.1254 0.68 0.8644 0 HLA-B 3106 A_24_P

13 13.46 0 0.1254 0.435 0.7506 0 IRF1 3659 A_23_P

9.11 9.46 0 0.1254 0.15 0.43466 0 FPR1 2357 A_23_P

9.55 10.52 0 0.1254 0.715 0.91489 0 RAB18 22931 A_23_P

10.64 10.84 0 0.1254 0.16 0.46339 0 PTCRA 171558 A_23_P

7.6 7.88 0 0.1254 0.1 0.37395 0 ARHGAP1 392 A_23_P

12.76 12.9 0 0.1254 0.26 0.59509 1 SDF4 51150 A_23_P

12.71 12.89 0 0.1254 0.86 0.96076 0 AMICA1 120425 A_24_P

10.94 11.78 0 0.1254 0.535 0.8114 0 CD79A 973 A_23_P

9.33 9.88 0 0.1254 0.13 0.40962 0 CD4 920 A_24_P

10.21 10.81 0 0.1254 0.18 0.47928 0 CTNNB1 1499 A_32_P

10.28 10.46 0 0.1254 0.525 0.8114 1 IGF2AS 51214 A_23_P

7.78 7.93 0 0.1254 0.94 1 0 XRCC6BP1 91419 A_24_P

7.05 6.96 0 0.1254 0.955 1 0 PAG1 55824 A_32_P

8.54 8.38 0 0.1254 0.59 0.8114 0 CCL3L3 414062 A_24_P

7.16 6.96 0 0.1254 0.955 1 0 DPP4 1803 A_24_P

7.04 6.9 0 0.1254 0.32 0.67843 0 TLN2 83660 A_32_P

7.57 7.42 0 0.1254 0.345 0.67843 0 RAC1 5879 A_23_P

12.63 12.45 0 0.1254 0.05 0.33742 0 LOC731884 731884 A_32_P

9.2 9.03 0 0.1254 0.575 0.8114 0 PEA15 8682 A_24_P

9.43 9.23 0 0.1254 0.435 0.7506 0 PLG 5340 A_32_P

7.33 7.19 0 0.1254 0.86 0.96076 0 CDH1 999 A_23_P

11.32 11.1 0 0.1254 0.265 0.59509 0 FKBP10 60681 A_23_P

13.53 13.4 0 0.1254 0.37 0.67843 0 RB1 5925 A_24_P

7.64 7.49 0 0.1254 0.095 0.37395 1 TAOK2 9344 A_23_P

8.61 8.45 0 0.1254 0.38 0.67843 0 DLL3 10683 A_23_P

7.66 7.48 0 0.1254 0.275 0.59509 1 MCAM 4162 A_23_P

10.61 10.45 0 0.1254 0.195 0.49367 0 PTGR1 22949 A_23_P

11.8 11.62 0 0.1254 0.65 0.8644 0 TCTN3 26123 A_32_P

11.84 11.62 0 0.1254 0.175 0.47521 0 CTNNAL1 8727 A_23_P

14.09 13.85 0 0.1254 0.6 0.8114 0 IGBP1 3476 A_23_P

10.06 9.93 0 0.1254 0.67 0.8644 0 SEMA5A 9037 A_24_P

9.34 9.17 0 0.1254 0.58 0.8114 0 CXCL12 6387 A_24_P

6.77 6.65 0 0.1254 0.6 0.8114 0 CMTM4 146223 A_32_P

11.34 11.22 0 0.1254 0.58 0.8114 0 APEX1 328 A_23_P

12.82 12.64 0 0.1254 0.735 0.91489 1 SLIT2 9353 A_32_P

7.86 7.78 0 0.1254 0.475 0.7506 0 CDH13 1012 A_32_P

11.21 11.05 0 0.1254 0.04 0.30732 0 SLTM 79811 A_23_P

11.67 11.5 0 0.1254 0.92 1 0 NLGN4X 57502 A_23_P

6.8 6.65 0 0.1254 0.505 0.8114 0 IFT140 9742 A_23_P

8.99 8.91 0 0.1254 0.565 0.8114 0 ATP5B 506 A_23_P

14.05 13.88 0 0.1254 0.965 1 0 PSMA4 5685 A_24_P

13.14 13.01 0 0.1254 0.15 0.43466 0 CASP4 837 A_23_P

12.63 12.75 0 0.1254 0.485 0.7506 0 RRAGA 10670 A_23_P

12.88 12.77 0 0.1254 0.095 0.37395 0 MYBPC3 4607 A_23_P

7.09 7.34 0 0.1254 0.475 0.7506 0 TREML1 340205 A_23_P

6.85 7.1 0 0.1254 0.365 0.67843 0 RARA 5914 A_23_P

7.76 8.06 0 0.1254 0.255 0.59509 0 NRP1 8829 A_23_P

6.93 7.05 0 0.1254 0.525 0.8114 0 SARNP 84324 A_23_P

13.96 13.84 0 0.1254 0.225 0.59509 0 IL17D 53342 A_23_P

8.47 8.37 0 0.1254 0.11 0.3862 0 ASB1 51665 A_32_P

9.87 9.79 0 0.1254 0.305 0.67843 0 TYROBP 7305 A_23_P

11.41 12.64 0 0.1254 0.67 0.8644 0 CASP9 842 A_24_P

12.07 11.96 0 0.1254 0.425 0.7506 0 IL13RA1 3597 A_23_P

10.58 10.49 0 0.1254 0.13 0.40962 0 HLA-B 3106 A_24_P

14.35 14.92 0 0.1254 0.87 0.96076 0 EXOC6 54536 A_32_P

7.2 7.09 0 0.1254 0.97 1 0 BUB3 9184 A_23_P

12.14 12.01 0 0.1254 0.81 0.96076 1 RTN4 57142 A_23_P

12.98 12.87 0 0.1254 0.105 0.3862 0 CADM3 57863 A_23_P

7.24 7.49 0 0.1254 0.49 0.7506 0 HIVEP3 59269 A_24_P

6.93 6.79 0 0.1254 0.725 0.91489 0 CLDN11 5010 A_23_P

7.24 7.47 0 0.1254 0.265 0.59509 0 MLL3 58508 A_23_P

8.46 8.35 0 0.1254 0.01 0.2608 0 PPFIBP1 8496 A_23_P

8.84 8.73 0 0.1254 0.295 0.59509 0 CFP 5199 A_23_P

9.84 10.77 0 0.1254 0.915 1 0 IL16 3603 A_24_P

7.24 7.15 0 0.1254 0.845 0.96076 0 ACVR1B 91 A_24_P

8.19 8.45 0 0.1254 0.39 0.67843 0 PTGER2 5732 A_23_P

8.44 8.31 0 0.1254 0.745 0.91489 0 BMP2 650 A_23_P

8.54 8.42 0 0.1254 0.62 0.8644 0 SON 6651 A_32_P

11.51 11.36 0 0.1254 0.84 0.96076 0 FRK 2444 A_23_P

6.72 6.56 0 0.1254 0.11 0.3862 0 TOPORS 10210 A_23_P

9.51 9.36 0 0.1254 0.26 0.59509 0 DYRK2 8445 A_24_P

8.8 8.66 0 0.1254 0.25 0.59509 0 TSLP 85480 A_23_P

8.1 8.03 0 0.1254 0.655 0.8644 0 CTNND1 1500 A_24_P

7.66 7.59 0 0.1254 0.19 0.47928 0 PRKG1 5592 A_32_P

6.79 7.13 0 0.1254 0.1 0.37395 0 C14orf153 84334 A_24_P

6.77 6.66 0 0.1254 0.205 0.59509 0 CD14 929 A_24_P

8.14 8.67 0 0.1254 0.855 0.96076 0 PLG 5340 A_23_P

7.28 7.15 0 0.1254 0.845 0.96076 0 CDC42SE2 56990 A_23_P

8.69 8.56 0 0.1254 0.31 0.67843 0 BCAP29 55973 A_32_P

7.74 7.62 0 0.1254 0.91 1 0 PPARA 5465 A_23_P

7.39 7.29 0 0.1254 0.8 0.91489 1 THBS2 7058 A_23_P

13.96 13.8 0 0.1254 0.255 0.59509 0 SEMA5A 9037 A_32_P

8.3 8.17 0 0.1254 0.775 0.91489 0 CMTM8 152189 A_23_P

9.13 8.93 0 0.1254 0.635 0.8644 0 MIB1 57534 A_32_P

7.54 7.42 0 0.1254 0.51 0.8114 0 FXR1 8087 A_24_P

9.31 9.18 0 0.1254 0.975 1 0 RIMS2 9699 A_23_P

7.39 7.22 0 0.1254 0.755 0.91489 0 LY86 9450 A_23_P

9.8 10.04 0 0.1254 0.185 0.47928 0 CYCS 54205 A_24_P

8.22 8.1 0 0.1254 0.05 0.33742 0 COL27A1 85301 A_23_P

12.74 12.61 0 0.1254 0.965 1 0 CRADD 8738 A_32_P

10.92 10.81 0 0.1254 0.95 1 0 HLA-F 3134 A_23_P

12.36 12.67 0 0.1254 0.3 0.59509 0 SLAMF7 57823 A_24_P

8.47 8.35 0 0.1254 0.62 0.8644 0 YWHAG 7532 A_24_P

14.51 14.33 0 0.1254 0.125 0.40962 0 INCENP 3619 A_23_P

10.79 10.65 0 0.1254 0.805 0.96076 0 DSTN 11034 A_23_P

13.7 13.58 0 0.1254 0.84 0.96076 0 JAKMIP1 152789 A_23_P

9.85 9.78 0 0.1254 0.07 0.33241 0 CBLB 868 A_23_P

9.84 9.71 0 0.1254 0.165 0.46339 0 ERC1 23085 A_23_P

7.1 6.97 0 0.1254 0.975 1 0 FLJ23834 222256 A_32_P

7.06 6.95 0 0.1254 0.35 0.67843 0 FUT8 2530 A_23_P

10.7 10.59 0 0.1254 0.35 0.67843 0 FN1 2335 A_24_P

8.71 8.6 0 0.1254 0.635 0.8644 0 FCER1G 2207 A_23_P

9.27 9.76 0 0.1254 0.56 0.8114 0 NF2 4771 A_23_P

7.13 7 0 0.1254 0.145 0.43466 0 PDCL3 79031 A_32_P

11.76 11.66 0 0.1254 0.95 1 0 IRS2 8660 A_24_P

7.15 7.28 0 0.1254 0.19 0.47928 1 TGM2 7052 A_24_P

8.25 8.45 0 0.1254 0.81 0.96076 0 COL15A1 1306 A_23_P

9.36 9.18 0 0.1254 0.035 0.30411 0 SMAD2 4087 A_32_P

7.01 6.92 0 0.1254 0.86 0.96076 0 E2F2 1870 A_23_P

7.66 8.06 0 0.1254 0.14 0.42106 0 ABL1 25 A_24_P

7.51 7.42 0 0.1254 0.155 0.45429 1 GLT25D2 23127 A_24_P

8.45 8.57 0 0.1254 0.525 0.8114 0 PRAM1 84106 A_23_P

8.39 8.73 0 0.1254 0.66 0.8644 0 PBX2 5089 A_32_P

7.55 7.69 0 0.1254 0.885 0.96076 0 EHD1 10938 A_23_P

12.1 12.27 0 0.1254 0.345 0.67843 0 ITFG3 83986 A_23_P

11.9 12.03 0 0.1254 0.34 0.67843 0 CNTNAP2 26047 A_23_P

8.56 8.68 0 0.1254 0.75 0.91489 0 THBS1 7057 A_24_P

9.65 9.83 0 0.1254 0.705 0.91489 0 UCP3 7352 A_24_P

7.45 7.84 0 0.1254 0.065 0.33241 1 SSTR3 6753 A_23_P

7.15 7.35 0 0.1254 0.185 0.47928 1 EXOC7 23265 A_23_P

9.67 9.79 0 0.1254 0.58 0.8114 0 CD300LB 124599 A_23_P

7.02 7.29 0 0.1254 0.685 0.8644 0 LAMC2 3918 A_23_P

7.78 7.88 0 0.1254 0.08 0.34601 0 RUNX1 861 A_24_P

7.47 7.84 0 0.1254 0.215 0.59509 0 TUBB 203068 A_32_P

14.06 14.15 0 0.1254 0.54 0.8114 0 B3GALNT1 8706 A_23_P

9.33 9.47 0 0.1254 0.21 0.59509 0 MPZL2 10205 A_24_P

6.99 6.77 0 0.1254 0.84 0.96076 0 SBDS 51119 A_32_P

10.42 10.51 0 0.1254 0.865 0.96076 0 LAT2 7462 A_23_P

10.67 10.96 0 0.1254 0.965 1 0 MLLT6 4302 A_32_P

11.01 11.16 0 0.1254 0.06 0.33241 0 LALBA 3906 A_23_P

6.52 6.94 0 0.1254 0.275 0.59509 0 PSMB2 5690 A_24_P

12.84 12.93 0 0.1254 0.7 0.8644 0 XRCC6 2547 A_32_P

7 6.88 0 0.1254 0.185 0.47928 1 NINJ2 4815 A_23_P

8.93 9.09 0 0.1254 0.6 0.8114 0 JAK3 3718 A_24_P

7.6 7.98 0 0.1254 0.09 0.36266 0 COL6A1 1291 A_32_P

7.38 7.55 0 0.1254 0.11 0.3862 0 LOC645166 645166 A_32_P

11.01 11.1 0 0.1254 0.835 0.96076 0 BCL6B 255877 A_23_P

6.7 6.62 0 0.1254 0.755 0.91489 0 ERCC2 2068 A_24_P

8.28 8.59 0 0.1254 0.09 0.36266 1 FCGR3A 2214 A_23_P

9.6 10.62 0 0.1254 0.785 0.91489 0 STX1A 6804 A_23_P

10.19 10.42 0 0.1254 0.01 0.2608 0 UMOD 7369 A_23_P

7.1 7.32 0 0.1254 0.025 0.28648 0 BNIP3L 665 A_23_P

11.6 11.74 0 0.1254 0.45 0.7506 0 NID2 22795 A_23_P

10.84 10.93 0 0.1254 0.57 0.8114 0 PSMB2 5690 A_23_P

11.96 12.16 0 0.1254 0.26 0.59509 0 KIR2DL4 3805 A_24_P

6.73 7.03 0 0.1254 0.32 0.67843 0 RAC2 5880 A_23_P

11.2 11.44 0 0.1254 0.405 0.7506 0 RBP4 5950 A_23_P

12.63 12.72 0 0.1254 0.49 0.7506 0 PDGFRB 5159 A_32_P

7.4 7.66 0 0.1254 0.105 0.3862 1 CDC42SE1 56882 A_23_P

9.99 10.19 0 0.1254 0.42 0.7506 0 FCN1 2219 A_23_P

8.04 8.74 0 0.1254 0.42 0.7506 0 IFITM2 10581 A_24_P

12.34 12.53 0 0.1254 0.575 0.8114 0 TNFAIP8L1 126282 A_24_P

7.08 6.9 0 0.1254 0.79 0.91489 0 TNFRSF11A 8792 A_23_P

7.39 7.19 0 0.1254 0.745 0.91489 0 APOL2 23780 A_24_P

11.23 11.51 0 0.1254 0.36 0.67843 0 LITAF 9516 A_23_P

10.27 10.38 0 0.1254 0.72 0.91489 0 TAOK2 9344 A_23_P

8.79 9.25 0 0.1254 0.175 0.47521 0 MINK1 50488 A_23_P

8.15 8.44 0 0.1254 0.07 0.33241 0 ITGB5 3693 A_23_P

11.96 12.05 0 0.1254 0.53 0.8114 0 CDSN 1041 A_23_P

7.17 7.46 0 0.1254 0.085 0.36266 0 LRP10 26020 A_23_P

11.57 11.66 0 0.1254 0.6 0.8114 0 XCL2 6846 A_23_P

6.93 6.79 0 0.1254 0.915 1 0 RHOA 387 A_24_P

10.45 10.59 0 0.1254 0.705 0.91489 0 HLA-DRB1 3123 A_24_P

9.57 10.01 0.005 0.1484 0.69 0.8644 0 FCN1 2219 A_23_P

11.05 12.26 0.005 0.1484 0.78 0.91489 0 7-Sep 989 A_24_P

9.46 9.57 0.005 0.1484 0.36 0.67843 0 MMP9 4318 A_23_P

8.47 8.69 0.005 0.1484 0.5 0.7506 0 MLXIPL 51085 A_24_P

8.89 9.37 0.005 0.1484 0.225 0.59509 0 RPSA 3921 A_32_P

9.35 9.43 0.005 0.1484 0.565 0.8114 0 HLA-A 3105 A_24_P

12.35 12.5 0.005 0.1484 0.11 0.3862 0 PHF17 79960 A_23_P

11.74 11.95 0.005 0.1484 0.015 0.2661 0 HLA-C 3107 A_23_P

14.13 14.69 0.005 0.1484 0.365 0.67843 0 CPLX2 10814 A_23_P

8.98 9.36 0.005 0.1484 0.05 0.33742 0 CASP8 841 A_23_P

8.73 8.99 0.005 0.1484 0.15 0.43466 0 BCL2 596 A_23_P

8.72 9.27 0.005 0.1484 0.125 0.40962 1 CACNB3 784 A_23_P

7.97 8.29 0.005 0.1484 0.16 0.46339 0 DGKZ 8525 A_23_P

9.41 9.61 0.005 0.1484 0.07 0.33241 0 PRKCD 5580 A_23_P

10.09 10.29 0.005 0.1484 0.745 0.91489 1 SMAD1 4086 A_23_P

6.96 6.85 0.005 0.1484 0.035 0.30411 0 SLFN5 162394 A_23_P

7.66 7.57 0.005 0.1484 0.015 0.2661 0 IGJ 3512 A_32_P

10.51 10.59 0.005 0.1484 0.43 0.7506 0 CCR9 10803 A_23_P

7.03 6.91 0.005 0.1484 0.245 0.59509 0 PPP2R1A 5518 A_32_P

7.43 7.32 0.005 0.1484 0.485 0.7506 0 DHRS2 10202 A_23_P

15.21 15.06 0.005 0.1484 0.455 0.7506 0 SGK1 6446 A_23_P

13.31 13.18 0.005 0.1484 0.62 0.8644 0 FNBP1L 54874 A_24_P

6.87 6.76 0.005 0.1484 0.115 0.39583 0 IK 3550 A_32_P

12.94 12.87 0.005 0.1484 0.455 0.7506 0 PSME1 5720 A_23_P

9.58 9.38 0.005 0.1484 0.825 0.96076 0 GPR98 84059 A_23_P

9.02 8.85 0.005 0.1484 0.48 0.7506 0 C1QTNF3 114899 A_23_P

8.46 8.32 0.005 0.1484 0.64 0.8644 0 IL2RG 3561 A_23_P

7.5 7.35 0.005 0.1484 0.345 0.67843 1 SNUPN 10073 A_24_P

9.26 9.09 0.005 0.1484 0.31 0.67843 2 STEAP2 261729 A_23_P

8.13 7.93 0.005 0.1484 0.45 0.7506 0 MAP4K4 9448 A_23_P

9.71 9.45 0.005 0.1484 0.86 0.96076 0 IFRD1 3475 A_24_P

11.09 10.88 0.005 0.1484 0.82 0.96076 0 NID1 4811 A_23_P

8.55 8.43 0.005 0.1484 0.68 0.8644 0 LPP 4026 A_23_P

8.44 8.3 0.005 0.1484 0.49 0.7506 0 SMURF2 64750 A_23_P

8.21 8.04 0.005 0.1484 0.665 0.8644 0 CAMK2D 817 A_24_P

10.72 10.55 0.005 0.1484 0.86 0.96076 0 TWIST1 7291 A_23_P

9.22 9.12 0.005 0.1484 0.14 0.42106 0 WNK1 65125 A_24_P

12.08 11.89 0.005 0.1484 0.195 0.49367 0 AP2S1 1175 A_24_P

11.17 11.06 0.005 0.1484 0.99 1 0 SIK1 150094 A_23_P

10.02 9.93 0.005 0.1484 0.955 1 0 PCDHB15 56121 A_23_P

7.7 7.58 0.005 0.1484 0.055 0.33742 0 PUF60 22827 A_23_P

12.99 12.84 0.005 0.1484 0.26 0.59509 0 RFFL 117584 A_23_P

7.82 7.71 0.005 0.1484 0.23 0.59509 0 DDR2 4921 A_32_P

8.18 8.07 0.005 0.1484 0.41 0.7506 0 HLA-B 3106 A_23_P

13.6 13.89 0.005 0.1484 1 1 0 FANCD2 2177 A_23_P

9.92 9.82 0.005 0.1484 0.095 0.37395 0 HDAC4 9759 A_23_P

9.91 9.82 0.005 0.1484 0.6 0.8114 0 ICAM3 3385 A_23_P

11.88 12.15 0.005 0.1484 0.675 0.8644 0 PHB 5245 A_23_P

11.56 11.48 0.005 0.1484 0.09 0.36266 0 MUC4 4585 A_24_P

7.16 7.53 0.005 0.1484 0.235 0.59509 0 PURB 5814 A_23_P

10.53 10.42 0.005 0.1484 0.175 0.47521 0 CLDN5 7122 A_23_P

7.21 7.47 0.005 0.1484 0.295 0.59509 0 SOCS4 122809 A_24_P

6.99 6.84 0.005 0.1484 0.015 0.2661 0 GHRHR 2692 A_24_P

7.16 7.44 0.005 0.1484 0.11 0.3862 1 PTGR2 145482 A_23_P

9.31 9.2 0.005 0.1484 0.785 0.91489 0 LENG8 114823 A_24_P

11.43 11.55 0.005 0.1484 0.555 0.8114 0 HLA-DOA 3111 A_24_P

8.42 8.84 0.005 0.1484 0.415 0.7506 0 ULBP2 80328 A_23_P

7.8 7.69 0.005 0.1484 0.805 0.96076 0 TGFB2 7042 A_24_P

6.9 6.8 0.005 0.1484 0.44 0.7506 0 MLLT1 4298 A_24_P

7.57 7.73 0.005 0.1484 0.075 0.34601 0 BCAM 4059 A_23_P

9.97 10.41 0.005 0.1484 0.165 0.46339 0 NF2 4771 A_23_P

13.22 13.1 0.005 0.1484 0.235 0.59509 0 IFI30 10437 A_23_P

12.68 12.85 0.005 0.1484 0.88 0.96076 0 FEN1 2237 A_24_P

11.69 11.6 0.005 0.1484 0.5 0.7506 1 COL27A1 85301 A_24_P

8.99 9.18 0.005 0.1484 0.055 0.33742 0 POGK 57645 A_24_P

10.54 10.44 0.005 0.1484 0.115 0.39583 0 MYADM 91663 A_24_P

7.97 8.16 0.005 0.1484 0.39 0.67843 0 EFNB1 1947 A_24_P

11.62 11.51 0.005 0.1484 0.25 0.59509 0 TYMP 1890 A_23_P

10.56 10.89 0.005 0.1484 0.995 1 0 TNFRSF19 55504 A_23_P

6.72 6.64 0.005 0.1484 0.175 0.47521 0 ADRBK1 156 A_23_P

6.63 6.74 0.005 0.1484 0.765 0.91489 0 EFNB2 1948 A_24_P

9.56 9.47 0.005 0.1484 0.395 0.67843 0 MRPS30 10884 A_23_P

10.45 10.31 0.005 0.1484 0.06 0.33241 0 FOXH1 8928 A_23_P

7.57 7.77 0.005 0.1484 0.13 0.40962 0 LAX1 54900 A_24_P

7.64 7.92 0.005 0.1484 0.575 0.8114 0 APOA4 337 A_24_P

6.81 6.94 0.005 0.1484 0.13 0.40962 0 HSPE1 3336 A_23_P

16.02 15.89 0.005 0.1484 0.64 0.8644 0 PLSCR1 5359 A_23_P

10.23 10.13 0.005 0.1484 0.455 0.7506 0 PEAR1 375033 A_24_P

7.29 7.49 0.005 0.1484 0.095 0.37395 0 DLC1 10395 A_23_P

12.69 12.56 0.005 0.1484 0.76 0.91489 0 SORL1 6653 A_23_P

11.91 12.09 0.005 0.1484 0.38 0.67843 0 CPLX1 10815 A_24_P

7.27 7.16 0.005 0.1484 0.93 1 0 B3GALNT1 8706 A_24_P

7.22 7.12 0.005 0.1484 0.61 0.8644 0 GYPC 2995 A_24_P

10.99 11.28 0.005 0.1484 0.52 0.8114 0 B3GNT5 84002 A_23_P

8.96 8.85 0.005 0.1484 0.05 0.33742 0 ICA1L 130026 A_23_P

6.86 6.74 0.005 0.1484 0.095 0.37395 0 C2 717 A_32_P

9.49 9.63 0.005 0.1484 0.02 0.27551 0 FCRL2 79368 A_24_P

6.71 6.9 0.005 0.1484 0.965 1 0 CCL24 6369 A_23_P

9.84 10.29 0.005 0.1484 0.09 0.36266 0 CDH16 1014 A_23_P

7.15 7 0.005 0.1484 0.46 0.7506 0 C9orf61 9413 A_32_P

6.8 6.71 0.005 0.1484 0.56 0.8114 2 SEMA3F 6405 A_23_P

6.92 7.18 0.005 0.1484 0.94 1 0 VHL 7428 A_23_P

15.97 16.18 0.005 0.1484 0.965 1 0 DIAPH2 1730 A_23_P

8.32 8.25 0.005 0.1484 0.285 0.59509 0 SNX3 8724 A_23_P

13.08 13.2 0.005 0.1484 0.14 0.42106 0 ZNF646 9726 A_24_P

10.83 10.9 0.005 0.1484 0.31 0.67843 2 PCDHB7 56129 A_24_P

7.8 7.88 0.005 0.1484 0.255 0.59509 0 SLC5A2 6524 A_23_P

8.66 8.95 0.005 0.1484 0.065 0.33241 0 AZU1 566 A_23_P

6.6 6.7 0.005 0.1484 0.135 0.42106 0 WNK1 65125 A_23_P

10.85 10.95 0.005 0.1484 0.025 0.28648 0 PGM5 5239 A_24_P

6.79 6.97 0.005 0.1484 0.175 0.47521 0 LTBR 4055 A_23_P

10.13 10.25 0.005 0.1484 0.215 0.59509 0 PNN 5411 A_23_P

13.29 13.36 0.005 0.1484 0.165 0.46339 0 HRH2 3274 A_23_P

6.93 7.12 0.005 0.1484 0.045 0.31994 0 PLEKHF1 79156 A_24_P

7.81 7.99 0.005 0.1484 0.005 0.25823 0 KYNU 8942 A_23_P

12.41 12.54 0.005 0.1484 0.44 0.7506 0 PLG 5340 A_24_P

7.44 7.61 0.005 0.1484 0.02 0.27551 0 MAP4K2 5871 A_24_P

7.24 7.4 0.005 0.1484 0.045 0.31994 0 CXCR5 643 A_23_P

6.65 6.76 0.005 0.1484 0.05 0.33742 0 SIGIRR 59307 A_23_P

10.53 10.68 0.005 0.1484 0.135 0.42106 0 CEACAM19 56971 A_23_P

8.66 9.03 0.005 0.1484 0.055 0.33742 0 HLA-E 3133 A_32_P

13.29 13.67 0.005 0.1484 0.305 0.67843 0 GZMM 3004 A_23_P

8.79 8.99 0.005 0.1484 0.01 0.2608 0 MAPK7 5598 A_23_P

9.67 9.81 0.005 0.1484 0.19 0.47928 0 HLA-DPB1 3115 A_23_P

10.52 10.72 0.005 0.1484 0.475 0.7506 0 SIGLEC5 8778 A_23_P

7.55 7.89 0.005 0.1484 0.945 1 0 PCDH9 5101 A_24_P

7.27 7.17 0.005 0.1484 0.555 0.8114 0 STX1A 6804 A_23_P

10.12 10.25 0.005 0.1484 0.425 0.7506 0 IGF2BP2 10644 A_23_P

7.15 6.99 0.005 0.1484 0.24 0.59509 0 HLA-DMB 3109 A_23_P

7.51 7.78 0.005 0.1484 0.925 1 0

indicates data missing or illegible when filed

APPENDIX C

TABLE S3 GEO Datasets used in meta-analysis of aging gene expression data GEO Data Set Pubmed Number or Series Title Species ID Source Chips GDS1278 Age effect on laryngeal Rattus McMullen CA, et al. 6 muscle norvegicus GDS1279 Age effect on extraocular Rattus McMullen CA, et al. 16 muscles norvegicus GDS1280 Age effect on central and Rattus McMullen CA, et al. 12 peripheral nervous norvegicus GDS1311 Age effect on Mus musculus 15919760 Godbout JP, et al. 12 lipopolysaccharide- induced neuroinflammation and GDS156 Muscle function and aging Homo sapiens 12204100 Welle S, et al. 12 (HG-U95A) GDS1961 Male and female thymi Mus musculus 17499630 Lustig A, et al. 40 response to aging and caloric restriction (A) GDS2019 Age effect on livers of Mus musculus DeFord JH, et al. 14 long-lived Snell dwarf GDS2082 Age effect on the Mus musculus 15169854 Verbitsky M, et al. 23 hippocampus GDS2612 Caloric restriction effect Mus musculus 17381838 Edwards MG, et al. 10 on aged skeletal muscle GDS2639 Aging and cognitive Rattus 17376971 Rowe WB, et al. 78 impairment: hippocampus norvegicus GDS2654 Neurological aging Mus musculus 15960800 Carter TA, et al. 9 models: retinas and GDS2681 Caloric restriction effect Mus musculus 16890326 Someya S, et al. 6 on aged cochlea GDS287 Muscle function and aging - Homo sapiens 12783983 Welle S, et al. 15 male (HG-U133A) GDS288 Muscle function and aging - Homo sapiens 12783983 Welle S, et al. 15 male (HG-U133B) GDS2929 Aging lungs and genetic Mus musculus 17726092 Misra V, et al. 15 background GDS2962 Male and female thymi Mus musculus 18081424 Lustig A, et al. 40 response to aging and caloric restriction (B) GDS355 Calorie restriction and Mus musculus Kayo T, et al. 10 aging (Mu11K-A) GDS356 Calorie restriction and Mus musculus Kayo T, et al. 10 aging (Mu11K-B) GDS399 Cardiac aging Rattus 12902548 Dobson JG, et al. 11 GDS40 Cardiac development, Mus musculus Schinke M, et al. 15 maturation and aging GDS472 Muscle function and aging - Homo sapiens Welle, et al. 15 female (HG-U133A) GDS473 Muscle function and aging - Homo sapiens Welle, et al. 15 female (HG-U133B) GDS520 Hippocampal aging and Rattus 12736351 Blalock EM, et al. 19 cognitive impairment norvegicus GDS583 Aging time course, normal Caenorhabditis 14730301 McCarroll SA, et al. 6 adult elegans GDS707 Aging brain: frontal cortex Homo sapiens 15190254 Lu T, et al. 22 expression profiles at various ages GSE11097 Coordinated Changes in Rattus Lee JS, et al. 21 Xenobiotic Metabolizing norvegicus Enzyme Gene Expression in Aging Male Rats: Brown Norway and F344 GSE11291 Effect of age, calorie Mus musculus 18523577 Barger JL, et al. 30 restriction and resveratrol on gene expression in mouse heart, brain, and skeletal muscle GSE11546 Age-related changes in Homo sapiens 18470533 Colantuoni C, et al. 33 the expression of schizophrenia susceptibility genes in the GSE12168 Aging Time course Caenorhabditis 18662544 Budovskaya YV, et 16 elegans al. GSE12290 Age-related behaviors Caenorhabditis 18778409 Golden TR, et al. 70 have distinct elegans transcriptional profiles in GSE12872 Drosophila melanogaster Drosophila 19164521 Neretti N, et al. 25 transcriptional profiling melanogaster over life span: Indy vs. GSE13496 Aging hematopoietic Homo sapiens 18596738 Stirewelt DL, et al. 10 progenitor/stem cells GSE3150 Aging Liver Profiles of the Mus musculus DeFord JH, et al. 21 Long Lived Prop-1 Mutant Mouse (Ames) and Wild Type Controls GSE3531 LTM in CA1 Aged versus Rattus 16829144 Burger C, et al. 79 young rats norvegicus GSE4821 Identification of putative Rattus Burger C, et al. 79 learning and memory norvegicus genes in the dentate gyrus of aged rats following the Morris Water Maze GSE5086 Transcriptional profile of Homo sapiens 16789832 Zahn JM, et al. 40 aging human muscle GSE6314 Temporal and Spatial Drosophila Yamaza H, et al. 55 Transcriptional Profiles of melanogaster Aging in Drosophila GSE6718 Transcriptional Response Rattus 17874999 Linford NJ, et al. 25 to Aging and Caloric norvegicus Restriction in Heart and GSE8409 Age Map, Cerebellum (A) Mus musculus 17988385 Zahn JM, et al. 40 GSE8410 Age Map, Cerebral Cortex Mus musculus 17988385 Zahn JM, et al. 40 GSE8412 Age Map, Spinal Cord (A) Mus musculus 17988385 Zahn JM, et al. 38 GSE8414 Age Map, Cerebellum (B) Mus musculus 17988385 Zahn JM, et al. 39 GSE8415 Age Map, Cerebral Cortex Mus musculus 17988385 Zahn JM, et al. 38 GSE8418 Age Map, Spinal Cord (B) Mus musculus 17988385 Zahn JM, et al. 41 GSE8419 Age Map, Striatum (B) Mus musculus 17988385 Zahn JM, et al. 40 GSE8479 Resistance Exercise Homo sapiens 17520024 Melov S, et al. 51 Reverses Aging in Human Skeletal Muscle GSE9103 Skeletal Muscle Transcript Homo sapiens Asmann YW, et al. 40 Profiles in Trained or Sedentary Young and Old Subjects GSE9419 The skeletal muscle Homo sapiens 17490972 Campbell WW, et 66 transcript profile reflects al. responses to inadequate protein intake in younger GSE9895 AGEMAP_Adrenals Mus musculus 16789832 Zahn JM, et al. 80 GSE9898 AGEMAP_Bone_Marrow Mus musculus 18081424 Zahn JM, et al. 72 GSE9900 AGEMAP_Eye Mus musculus 18081424 Zahn JM, et al. 80 GSE9901 AGEMAP_Gonads Mus musculus 16789832 Zahn JM, et al. 77 GSE9902 AGEMAP_Heart Mus musculus 16789832 Zahn JM, et al. 76 GSE9904 AGEMAP_Kidney Mus musculus 16789832 Zahn JM, et al. 80 GSE9905 AGEMAP_Liver Mus musculus 18081424 Zahn JM, et al. 64 GSE9906 AGEMAP_Lung Mus musculus 16789832 Zahn JM, et al. 80 GSE9907 AGEMAP_Skeletal_Muscle Mus musculus 18081424 Zahn JM, et al. 80 GSE9908 AGEMAP_Spleen Mus musculus 18081424 Zahn JM, et al. 80

APPENDIX D

TABLE S4 Genes found to be significantly associated with age in the meta-analysis Entrez ID Name MetaEffect pvalFisher 68031 C3 0.337698315 1.10E−54 7750 RT1-Ba 0.196164486 1.06E−41 1880 Gpnmb 0.643641429 1.01E−37 2974 Fcgr2b 0.243994532 2.05E−34 16958 Igj 0.226477271 3.56E−32 17012 1100001E

0.849789673 4.49E−32 20867 Ctss 0.152554449 3.55E−31 9962 CXorf57 0.325268282 6.96E−27 86179 EG665378 1.104731656 9.48E−27 1603 RT1-Bb 0.160732706 2.23E−25 36030 C4b 0.261099138 5.33E−24 56810 Lrp1b 0.30257626 5.74E−24 5109 Adamts5 0.251108456 6.79E−24 68066 Hbb 0.164149192 7.36E−24 90902 Usp54 0.186061881 3.01E−23 14126 Il33 0.215106418 6.57E−23 7924 S100a4 0.208560953 1.86E−21 7839 Mlf1 −0.2592617 8.04E−21 113759 C21orf7 0.768001812 7.61E−20 115591 LOC25924

−0.15443516 1.27E−19 23032 Fam46a 0.180448732 1.38E−19 1431 Ctgf 0.183450344 5.03E−18 31070 Glra2 −0.15727832 5.78E−18 49424 CCDC69 −0.204656 1.73E−16 7986 Tyrobp 0.281565935 1.99E−16 2000 Plek 0.182525947 2.35E−16 23519 Acsf2 −0.36717971 2.72E−16 37584 Hoxb2 −0.28593823 1.51E−15 49543 ZNF415 −0.25527055 2.94E−15 122149 HMGN2 0.278687741 8.90E−15 88734 MT1X 0.304942233 9.85E−15 108195 NPIP 0.210485047 2.02E−14 2086 Pros28.1 0.212491471 2.18E−14 69153 Ptpla −0.34183304 4.75E−14 89678 LOC68500

1.084414575 4.78E−14 120336 LOC49978

0.216224302 5.11E−14 49694 Cxcl16 0.218628389 6.86E−14 82588 RGD15599 −0.15420995 7.29E−14 56300 CG13384 0.278803929 1.05E−13 7309 Mpzl2 0.176061389 2.81E−13 65299 Tmtc1 0.154398135 3.08E−13 74448 LOC28691

−0.18157704 4.15E−13 41282 Erbb2ip 0.168449838 4.66E−13 49949 COL21A1 0.199777973 8.60E−13 88747 C10orf116 0.380945602 2.17E−12 38171 Ifi30 0.262554903 2.20E−12 104063 UQCRH −0.27138499 3.75E−12 9413 Clec4a3 0.635951202 4.74E−12 88538 1700034I2 −0.19778363 5.48E−12 5782 Lace1 −0.19706732 8.82E−12 2236 Clec11a −0.18548667 1.25E−11 1209 Irf7 0.177331413 1.36E−11 17048 Ttc18 0.200712085 1.49E−11 76450 Cml3 0.36115736 2.07E−11 15446 Asb12 −0.36585936 3.52E−11 477 Fcgr3a 0.320924509 3.61E−11 20453 Cfd 0.162628176 3.63E−11 90224 1500009L1 0.225854306 9.44E−11 17057 Spata18 0.155521865 9.97E−11 115689 Plscr2 0.437399565 2.77E−10 9294 Pla1a 0.151688359 3.57E−10 18882 Paqr9 −0.19890688 3.82E−10 40707 Opn3 −0.17691302 3.90E−10 89046 RGD15641 0.185419884 4.30E−10 7945 Slfn2 0.421614816 4.39E−10 121641 His3.3A 0.219066526 4.64E−10 79796 LOC68975

−0.2593191 8.52E−10 8332 Hook2 −0.1705913 1.29E−09 108191 MT1H 0.210737894 1.72E−09 16012 Frmd3 −0.16181809 1.91E−09 35310 3-Mar −0.15429759 2.06E−09 87124 Pcdhb9 0.254572988 3.36E−09 105677 YWHAQ 0.171385197 4.10E−09 11093 Fn3krp 0.202668204 4.37E−09 11509 Ccdc28b −0.21674847 4.68E−09 87898 ISCA1 −0.19555157 5.40E−09 45124 Gcom1 0.169362212 5.83E−09 74413 E2f3 −0.15512234 8.46E−09 48326 G1p2 0.329823574 1.10E−08 37689 PTMA 0.166331587 1.20E−08 9135 TRIM58 0.237072147 1.31E−08 23499 Synpo2l 0.24111956 1.49E−08 9574 Pcdh12 −0.22442615 1.78E−08 27392 Cpne2 0.233138906 1.79E−08 12698 Ddit4l −0.16390882 2.06E−08 75853 Cyp4x1 0.219081962 2.92E−08 114241 RGD15594 0.469297715 3.25E−08 72226 Zfp454 0.29786873 3.38E−08 55916 S100a11 0.157104104 5.53E−08 14286 Galntl2 0.219172594 7.10E−08 294 Sox9 0.252846332 8.50E−08 104370 ZNF492 0.238974473 9.47E−08 122101 C14orf2 −0.1545888 1.10E−07 121604 DUSP13 −0.3154509 1.13E−07 62161 Vangl2 −0.18404987 1.44E−07 19108 Dhrs7c −0.21508803 1.55E−07 45432 Slfn8 0.243086196 2.01E−07 48388 MT2A 0.299104826 3.01E−07 5353 Pdss1 −0.1508792 3.71E−07 77713 LOC36022

0.150600586 3.98E−07 8835 FAM38A 0.252755946 4.57E−07 25079 TPPP2 −0.16214316 7.69E−07 86882 Fmo2 0.23321182 7.99E−07 49517 TRMT61B −0.20121551 1.07E−06 123533 RGD13101 −0.40076548 1.11E−06 19274 4933405L1 −0.24082886 1.12E−06 86733 MGC10882 0.279660777 1.37E−06 56783 LOC31072

0.267238671 1.65E−06 10073 Pnmal1 0.295057188 2.08E−06 89164 isg12(b) 0.189563208 2.15E−06 10641 CTNNBIP1 −0.25394574 2.27E−06 39074 Nmnat1 −0.15689057 2.51E−06 66117 MYH7B 0.323225125 3.03E−06 48468 H28 0.194466507 3.23E−06 74438 Ifi204 0.216986862 3.34E−06 7014 EG226654 0.267725488 3.80E−06 85555 1700019N −0.35184516 4.34E−06 19952 Efcab7 0.15813991 4.69E−06 8024 Hcst 0.172404007 5.13E−06 7392 Kcnu1 −0.27873757 5.23E−06 23217 Plscr4 0.20548157 5.91E−06 17562 Ankle1 0.217270121 9.29E−06 68443 CLEC2B 0.204602687 9.30E−06 826 RGD13105 0.170957726 9.55E−06 9927 Fam70a 0.159236473 9.96E−06 86122 ISOC2 −0.21966312 1.04E−05 4665 Ubd 0.158771035 1.06E−05 103871 RGD13079 −0.18158672 1.43E−05 122195 1700054F2 −0.17122413 1.49E−05 45975 RGD13093 0.188776766 1.61E−05 28424 Rasef 0.185265697 1.66E−05 70768 Herc6 0.164936064 1.86E−05 16320 Cthrc1 −0.22905115 2.18E−05 118004 1700019G

0.192558616 2.52E−05 88921 C1qtnf3 −0.26565138 4.28E−05 117949 Fcn1 0.296439068 4.59E−05 121796 Krtap4-2 −0.48676484 4.66E−05 86269 Stfa2l3 0.539695764 5.11E−05 8908 Galnac4s-

−0.15004653 5.67E−05 22708 Itgb1bp2 −0.1846864 5.89E−05 12732 Tmem177 −0.15887907 8.44E−05 56944 Rtp4 0.160669645 8.54E−05 18680 Tmem52 0.194064654 8.72E−05 17571 Kbtbd5 0.316607601 9.22E−05 85034 OTTMUSG

−0.15381647 9.44E−05 9726 Gramd1c 0.157603931 9.59E−05 10813 Alpk3 0.1854543 0.00011733 84858 Cd209b 0.231577687 0.00013048 49905 1700074P

−0.30179196 0.00014641 76446 Tsga13 −0.16383325 0.00014714 86705 LOC69117

−0.22412126 0.0001552 114502 LOC68515

0.394921169 0.00016499 18252 Fsd2 −0.16439316 0.0001684 71779 Rsph4a 0.255594277 0.00019155 34940 Arid5a 0.156559299 0.00025282 16823 CG9996 0.232308435 0.00025503 77416 Mlkl −0.16899747 0.00034472 12257 4930547C

1.950401446 0.00048183 41271 Arhgap15 0.159114218 0.00048941 19144 Fam171a2 −0.18584737 0.00052079 49710 TTC31 0.179167307 0.00058897 79726 Doxl1 −0.19722464 0.00061038 117975 ZNF432 0.213393951 0.00062803 110822 Klra5 0.18662964 0.00067557 89168 ZNF323 0.222940842 0.00070422 9555 Ninj2 0.154045269 0.0007144 35542 E030049G

−0.32681836 0.0007853 69257 ERMAP 0.172273481 0.00078899 50475 Alpk2 0.152879973 0.00085675 117700 ZNF267 0.1545496 0.00087049 18691 6430537H

0.153146801 0.00094589 17794 Klre1 −0.16554649 0.00098146 78018 Lrrc69 0.152806524 0.00108119 10471 MOSPD1 −0.15083294 0.00117142 108186 HMGN1 0.170483349 0.00118704 28471 RGD15631 0.177024178 0.0012595 10590 1810011O

−0.18929868 0.00130599 10416 4933403G

−0.30079696 0.00132841 75166 Pmaip1 0.390056763 0.00137565 18842 2310010M −0.16617861 0.0014787 65996 BC046404 −0.18761865 0.00157999 65257 Ip6k3 0.183436928 0.00173745 22993 Gypc −0.15892467 0.00190704 81055 Slc16a12 0.173590885 0.00204682 48124 Ppp1r3a −0.16723044 0.00209565 119893 Ces6 −0.15031123 0.00212561 18692 Dpy19l3 −0.15647733 0.00214371 56428 Ppm1a −0.15028605 0.0021799 8897 Tecpr2 0.191902469 0.00251988 88945 BC043301 −0.1536364 0.00260783 86703 Ng23 −0.19533328 0.00267018 47588 MGC1162

−0.1949287 0.00274781 113783 Itgb1bp3 0.316801607 0.0029 41378 Olfr1509 −0.18984245 0.00312148 104345 LOC68023

0.420756428 0.00325828 114519 Cd209g 0.224085149 0.00341367 27072 A330049M 0.215087101 0.00348459 12281 RGD13080 −0.21493136 0.00397285 77326 Zfp52 0.33674368 0.0039854 99855 Agmat −0.15017764 0.0047176 110478 Olfr672 0.482514016 0.00499443 35234 Pddc1 0.160100112 0.0054081 75198 Ankrd36 0.35318104 0.00592135 11488 Smtnl1 0.207571119 0.00597194 18544 Rnf222 0.531926369 0.00728218 110771 Svs3 −0.21042565 0.00775244 10957 Cd200r1 0.33606348 0.00820976 84597 Tusc1 −0.21056139 0.00826404 103867 4933415F

0.174474914 0.00840595 77918 1700065l1 −0.25231707 0.00870332 122178 Cyp2j5 0.168201503 0.00870845 23416 Slco1a6 −0.18459302 0.00938508 104304 Psbpc1 −0.24382829 0.00950761 32697 Nphp3 0.178084932 0.00952455

indicates data missing or illegible when filed

APPENDIX E

TABLE S5 Network cluster Serum membership cytokines Chemokines TH1 INF-A2 Eotaxin INF-G IL-12p40 Th2 II-4 IP-10 IL-5 IL-7 Gene Entrez Gene Gene Expression Probe ID ID Symbol Description GC1 A_23_P107735 973 CD79A CD79a molecule, immunoglobulin- associated alpha A_23_P116387 3619 INCENP inner centromere protein antigens 135/155 kDa A_23_P116765 3906 LALBA lactalbumin, alpha- A_23_P125990 1870 E2F2 E2F transcription factor 2 A_23_P127385 4607 MYBPC3 myosin binding protein C, cardiac A_23_P130836 3004 GZMM granzyme M (lymphocyte metase 1) A_23_P132115 150094 SIK1 salt-inducible kinase 1 A_23_P133665 2444 FRK fyn-related kinase A_23_P140057 55504 TNFRSF19 tumor necrosis factor receptor superfamily, member 19 A_23_P145264 3134 HLA-F major histocompatibility complex, class I, F A_23_P15369 124599 CD300LB CD300 molecule-like family member b A_23_P156550 340205 TREML1 triggering receptor expressed on myeloid cells-like 1 A_23_P158775 7369 UMOD uromodulin A_23_P160849 2207 FCER1G Fc fragment of IgE, high affinity I, receptor for; gamma polypeptide A_23_P164307 50488 MINK1 misshapen-like kinase 1 (zebrafish) A_23_P167537 10814 CPLX2 complexin 2 A_23_P17224 130026 ICA1L islet cell autoantigen 1, 69 kDa-like A_23_P201156 57863 CADM3 cell adhesion molecule 3 A_23_P202667 156 ADRBK1 adrenergic, beta, receptor kinase 1 A_23_P203215 643 CXCR5 chemokine (C—X—C motif) receptor 5 A_23_P207842 5914 RARA retinoic acid receptor, alpha A_23_P208132 596 BCL2 B-cell CLL/lymphoma 2 A_23_P209389 841 CASP8 caspase 8, apoptosis- related cysteine peptidase A_23_P215491 6369 CCL24 chemokine (C-C motif) ligand 24 A_23_P218269 9344 TAOK2 TAO kinase 2 A_23_P258377 23085 ERC1 ELKS/RAB6- interacting/CAST family member 1 A_23_P29800 5010 CLDN11 claudin 11 A_23_P306730 5465 PPARA peroxisome proliferator- activated receptor alpha A_23_P30755 171558 PTCRA pre T-cell antigen receptor alpha A_23_P324813 255877 BCL6B B-cell CLL/lymphoma 6, member B (zinc finger protein) A_23_P325991 4771 NF2 neurofibromin 2 (merlin) A_23_P334271 4086 SMAD1 SMAD family member 1 A_23_P364592 57502 NLGN4X neuroligin 4, X-linked A_23_P371794 784 CACNB3 calcium channel, voltage- dependent, beta 3 subunit A_23_P390518 8792 TNFRSF11A tumor necrosis factor receptor superfamily, member 11a, NFKB activator A_23_P398574 4059 BCAM basal cell adhesion molecule (Lutheran blood group) A_23_P402899 162394 SLFN5 schlafen family member 5 A_23_P408095 11034 DSTN destrin (actin depolymerizing factor) A_23_P411277 6524 SLC5A2 solute carrier family 5 (sodium/glucose cotransporter), member 2 A_23_P41166 8706 B3GALNT1 beta-1,3-N- acetylgalactosaminyltransferase 1 (globoside blood group) A_23_P430764 56990 CDC42SE2 CDC42 small effector 2 A_23_P48109 4815 NINJ2 ninjurin 2 A_23_P6321 7122 CLDN5 claudin 5 A_23_P68910 6753 SSTR3 somatostatin receptor 3 A_23_P70520 1041 CDSN corneodesmosin A_23_P7535 3274 HRH2 histamine receptor H2 A_23_P78526 56971 CEACAM19 carcinoembryonic antigen- related cell adhesion molecule 19 A_23_P82959 8928 FOXH1 forkhead box H1 A_23_P86390 8829 NRP1 neuropilin 1 A_23_P95672 10644 IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2 A_24_P134195 91663 MYADM myeloid-associated differentiation marker A_24_P139901 2995 GYPC glycophorin C (Gerbich blood group) A_24_P151295 4298 MLLT1 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 1 A_24_P17048 2692 GHRHR growth hormone releasing hormone receptor A_24_P194068 79156 PLEKHF1 pleckstrin homology domain containing, family F (with FYVE domain) member 1 A_24_P207003 8660 IRS2 insulin receptor substrate 2 A_24_P209389 51085 MLXIPL MLX interacting protein- like A_24_P22174 84334 C14orf153 chromosome 14 open reading frame 153 A_24_P239183 4585 MUC4 mucin 4, cell surface associated A_24_P240487 5340 PLG plasminogen A_24_P252934 337 APOA4 apolipoprotein A-IV A_24_P282416 25 ABL1 c-abl oncogene 1, receptor tyrosine kinase A_24_P288298 3805 KIR2DL4 killer cell immunoglobulin- like receptor, two domains, long cytoplasmic tail, 4 A_24_P291278 54900 LAX1 lymphocyte transmembrane adaptor 1 A_24_P292470 7352 UCP3 uncoupling protein 3 (mitochondrial, proton carrier) A_24_P295999 920 CD4 CD4 molecule A_24_P308096 3718 JAK3 Janus kinase 3 A_24_P341897 91 ACVR1B activin A receptor, type IB A_24_P354800 3111 HLA-DOA major histocompatibility complex, class II, DO alpha A_24_P363896 85301 COL27A1 collagen, type XXVII, alpha 1 A_24_P366967 54874 FNBP1L formin binding protein 1- like A_24_P385326 375033 PEAR1 platelet endothelial aggregation receptor 1 A_24_P38702 159296 NKX2-3 NK2 transcription factor related, locus 3 (Drosophila) A_24_P401990 2068 ERCC2 excision repair cross- complementing rodent repair deficiency, complementation group 2 A_24_P50767 5871 MAP4K2 mitogen-activated protein kinase kinase kinase kinase 2 A_24_P881527 1500 CTNND1 catenin (cadherin- associated protein), delta A_24_P917783 861 RUNX1 runt-related transcription factor 1 A_32_P150735 55973 BCAP29 B-cell receptor-associated protein 29 A_32_P183609 51665 ASB1 ankyrin repeat and SOCS box-containing 1 A_32_P187875 1499 CTNNB1 catenin (cadherin- associated protein), beta 1, 88 kDa A_32_P197942 222256 FLJ23834 hypothetical protein FLJ23834 A_32_P215404 5159 PDGFRB platelet-derived growth factor receptor, beta polypeptide A_32_P460973 3133 HLA-E major histocompatibility complex, class I, E A_32_P6062 5592 PRKG1 protein kinase, cGMP- dependent, type I A_32_P72622 1291 COL6A1 collagen, type VI, alpha 1 GC2 A_23_P100704 5598 MAPK7 mitogen-activated protein kinase 7 A_23_P102192 9448 MAP4K4 mitogen-activated protein kinase kinase kinase kinase 4 A_23_P112554 1306 COL15A1 collagen, type XV, alpha 1 A_23_P119562 1675 CFD complement factor D (adipsin) A_23_P127627 8525 DGKZ diacylglycerol kinase, zeta 104 kDa A_23_P134517 5814 PURB purine-rich element binding protein B A_23_P144054 5580 PRKCD protein kinase C, delta A_23_P164691 3385 ICAM3 intercellular adhesion molecule 3 A_23_P166633 3693 ITGB5 integrin, beta 5 A_23_P168419 58508 MLL3 myeloid/lymphoid or mixed-lineage leukemia 3 A_23_P168556 6804 STX1A syntaxin 1A (brain) A_23_P169117 10670 RRAGA Ras-related GTP binding A A_23_P170058 5690 PSMB2 proteasome (prosome, macropain) subunit, beta type, 2 A_23_P18372 84002 B3GNT5 UDP-GlcNAc:betaGal beta- 1,3-N- acetylglucosaminyltransferase 5 A_23_P19134 84059 GPR98 G protein-coupled receptor 98 A_23_P201636 3918 LAMC2 laminin, gamma 2 A_23_P205499 26020 LRP10 low density lipoprotein receptor-related protein 10 A_23_P206359 999 CDH1 cadherin 1, type 1, E- cadherin (epithelial) A_23_P212360 10803 CCR9 chemokine (C-C motif) receptor 9 A_23_P218770 5880 RAC2 ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) A_23_P250701 65125 WNK1 WNK lysine deficient protein kinase 1 A_23_P251051 4771 NF2 neurofibromin 2 (merlin) A_23_P252362 10884 MRPS30 mitochondrial ribosomal protein S30 A_23_P35912 837 CASP4 caspase 4, apoptosis- related cysteine peptidase A_23_P40174 4318 MMP9 matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa type IV collagenase) A_23_P428260 261729 STEAP2 six transmembrane epithelial antigen of the prostate 2 A_23_P47867 8496 PPFIBP1 PTPRF interacting protein, binding protein 1 (liprin beta 1) A_23_P52647 10938 EHD1 EH-domain containing 1 A_23_P53557 4055 LTBR lymphotoxin beta receptor (TNFR superfamily, member 3) A_23_P56898 8942 KYNU kynureninase (L- kynurenine hydrolase) A_23_P56933 57142 RTN4 reticulon 4 A_23_P6878 6405 SEMA3F sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F A_23_P75283 5950 RBP4 retinol binding protein 4, plasma A_23_P82420 6804 STX1A syntaxin 1A (brain) A_23_P84344 59307 SIGIRR single immunoglobulin and toll-interleukin 1 receptor (TIR) domain A_23_P84399 26047 CNTNAP2 contactin associated protein-like 2 A_23_P87049 6653 SORL1 sortilin-related receptor, L(DLR class) A repeats- containing A_23_P91802 1890 TYMP thymidine phosphorylase A_24_P102636 5925 RB1 retinoblastoma 1 A_24_P106681 7532 YWHAG tyrosine 3- monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide A_24_P137897 3475 IFRD1 interferon-related developmental regulator 1 A_24_P174550 387 RHOA ras homolog gene family, member A A_24_P187218 5101 PCDH9 protocadherin 9 A_24_P243373 56129 PCDHB7 protocadherin beta 7 A_24_P254949 5239 PGM5 phosphoglucomutase 5 A_24_P287043 10581 IFITM2 interferon induced transmembrane protein 2 (1-8D) A_24_P376483 3105 HLA-A major histocompatibility complex, class I, A A_24_P402438 7042 TGFB2 transforming growth factor, beta 2 A_24_P407717 2885 GRB2 growth factor receptor- bound protein 2 A_24_P48898 23780 APOL2 apolipoprotein L, 2 A_24_P62505 23127 GLT25D2 glycosyltransferase 25 domain containing 2 A_24_P769359 65125 WNK1 WNK lysine deficient protein kinase 1 A_24_P90637 122809 SOCS4 suppressor of cytokine signaling 4 A_24_P926770 26020 LRP10 low density lipoprotein receptor-related protein 10 A_24_P944054 6387 CXCL12 chemokine (C—X—C motif) ligand 12 (stromal cell- derived factor 1) A_24_P97104 1803 DPP4 dipeptidyl-peptidase 4 A_32_P109002 4087 SMAD2 SMAD family member 2 A_32_P132748 731884 LOC731884 similar to programmed cell death 6 interacting protein A_32_P162187 717 C2 complement component 2 A_32_P206123 5340 PLG plasminogen A_32_P43664 3512 IGJ immunoglobulin J polypeptide, linker protein for immunoglobulin alpha and mu polypeptides A_32_P61684 55824 PAG1 phosphoprotein associated with glycosphingolipid microdomains 1 A_32_P78528 203068 TUBB tubulin, beta A_32_P85999 1012 CDH13 cadherin 13, H-cadherin (heart) A_32_P98683 4302 MLLT6 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 6 GC3 A_23_P100556 23265 EXOC7 exocyst complex component 7 A_23_P116435 51214 IGF2AS insulin-like growth factor 2 antisense A_23_P121851 56121 PCDHB15 protocadherin beta 15 A_23_P130040 5245 PHB prohibitin A_23_P137196 3597 IL13RA1 interleukin 13 receptor, alpha 1 A_23_P143994 2177 FANCD2 Fanconi anemia, complementation group D2 A_23_P144274 152789 JAKMIP1 Janus kinase and microtubule interacting protein 1 A_23_P151710 5732 PTGER2 prostaglandin E receptor 2 (subtype EP2), 53 kDa A_23_P153741 566 AZU1 azurocidin 1 A_23_P15727 60681 FKBP10 FK506 binding protein 10, 65 kDa A_23_P171255 3476 IGBP1 immunoglobulin (CD79A) binding protein 1 A_23_P210048 9759 HDAC4 histone deacetylase 4 A_23_P212715 868 CBLB Cas-Br-M (murine) ecotropic retroviral transforming sequence b A_23_P215406 5879 RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) A_23_P30693 5340 PLG plasminogen A_23_P313632 2530 FUT8 fucosyltransferase 8 (alpha (1,6) fucosyltransferase) A_23_P32217 10210 TOPORS topoisomerase I binding, arginine/serine-rich A_23_P345692 53342 IL17D interleukin 17D A_23_P40880 152189 CMTM8 CKLF-like MARVEL transmembrane domain containing 8 A_23_P43946 84324 SARNP SAP domain containing ribonucleoprotein A_23_P46924 9184 BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast) A_23_P48713 145482 PTGR2 prostaglandin reductase 2 A_23_P56922 3336 HSPE1 heat shock 10 kDa protein 1 (chaperonin 10) A_23_P62021 7058 THBS2 thrombospondin 2 A_23_P69109 5359 PLSCR1 phospholipid scramblase 1 A_23_P70688 9450 LY86 lymphocyte antigen 86 A_23_P85004 1730 DIAPH2 diaphanous homolog 2 (Drosophila) A_24_P111342 842 CASP9 caspase 9, apoptosis- related cysteine peptidase A_24_P124992 5685 PSMA4 proteasome (prosome, macropain) subunit, alpha type, 4 A_24_P142118 7057 THBS1 thrombospondin 1 A_24_P161933 3106 HLA-B major histocompatibility complex, class I, B A_24_P228130 414062 CCL3L3 chemokine (C-C motif) ligand 3-like 3 A_24_P286465 5814 PURB purine-rich element binding protein B A_24_P291973 989 7-Sep septin 7 A_24_P29665 54205 CYCS cytochrome c, somatic A_24_P319647 79368 FCRL2 Fc receptor-like 2 A_24_P353638 57823 SLAMF7 SLAM family member 7 A_24_P355944 1948 EFNB2 ephrin-B2 A_24_P40055 114823 LENG8 leukocyte receptor cluster (LRC) member 8 A_24_P876734 59269 HIVEP3 human immunodeficiency virus type I enhancer binding protein 3 A_24_P923251 7052 TGM2 transglutaminase 2 (C polypeptide, protein- glutamine-gamma- glutamyltransferase) A_24_P942786 8445 DYRK2 dual-specificity tyrosine- (Y)-phosphorylation regulated kinase 2 A_32_P141664 5089 PBX2 pre-B-cell leukemia homeobox 2 A_32_P222335 3921 RPSA ribosomal protein SA A_32_P230838 2547 XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 A_32_P29759 3550 IK IK cytokine, down- regulator of HLA II A_32_P36217 6651 SON SON DNA binding protein A_32_P58280 54536 EXOC6 exocyst complex component 6 GC4 A_23_P100754 64750 SMURF2 SMAD specific E3 ubiquitin protein ligase 2 A_23_P113716 3107 HLA-C major histocompatibility complex, class I, C A_23_P122068 114899 C1QTNF3 C1q and tumor necrosis factor related protein 3 A_23_P125107 3106 HLA-B major histocompatibility complex, class I, B A_23_P132611 7428 VHL von Hippel-Lindau tumor suppressor A_23_P148473 3561 IL2RG interleukin 2 receptor, gamma (severe combined immunodeficiency) A_23_P151614 5720 PSME1 proteasome (prosome, macropain) activator subunit 1 (PA28 alpha) A_23_P151649 328 APEX1 APEX nuclease (multifunctional DNA repair enzyme) 1 A_23_P157795 8727 CTNNAL1 catenin (cadherin- associated protein), alpha- like 1 A_23_P157809 22949 PTGR1 prostaglandin reductase 1 A_23_P162171 4162 MCAM melanoma cell adhesion molecule A_23_P163087 22795 NID2 nidogen 2 (osteonidogen) A_23_P16438 10683 DLL3 delta-like 3 (Drosophila) A_23_P19673 6446 SGK1 serum/glucocorticoid regulated kinase 1 A_23_P200928 4811 NID1 nidogen 1 A_23_P201338 51150 SDF4 stromal cell derived factor 4 A_23_P251118 4026 LPP LIM domain containing preferred translocation partner in lipoma A_23_P258769 3115 HLA-DPB1 major histocompatibility complex, class II, DP beta 1 A_23_P26094 79811 SLTM SAFB-like, transcription modulator A_23_P308673 9344 TAOK2 TAO kinase 2 A_23_P314070 392 ARHGAP1 Rho GTPase activating protein 1 A_23_P320883 56882 CDC42SE1 CDC42 small effector 1 A_23_P321501 10202 DHRS2 dehydrogenase/reductase (SDR family) member 2 A_23_P330209 117584 RFFL ring finger and FYVE-like domain containing 1 A_23_P33216 506 ATP5B ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide A_23_P3532 9516 LITAF lipopolysaccharide- induced TNF factor A_23_P408708 665 BNIP3L BCL2/adenovirus E1B 19 kDa interacting protein 3-like A_23_P42498 8724 SNX3 sorting nexin 3 A_23_P71067 7291 TWIST1 twist homolog 1 (Drosophila) A_23_P9756 22827 PUF60 poly-U binding splicing factor 60 KDa A_23_P99582 5411 PNN pinin, desmosome associated protein A_24_P113674 3106 HLA-B major histocompatibility complex, class I, B A_24_P114739 817 CAMK2D calcium/calmodulin- dependent protein kinase II delta A_24_P181506 9726 ZNF646 zinc finger protein 646 A_24_P27412 10073 SNUPN snurportin 1 A_24_P284893 5690 PSMB2 proteasome (prosome, macropain) subunit, beta type, 2 A_24_P336754 4170 MCL1 myeloid cell leukemia sequence 1 (BCL2-related) A_24_P410952 8682 PEA15 phosphoprotein enriched in astrocytes 15 A_24_P418044 3137 HLA-J major histocompatibility complex, class I, J (pseudogene) A_24_P73599 3603 IL16 interleukin 16 (lymphocyte chemoattractant factor) A_24_P912799 9037 SEMA5A sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A A_24_P927404 91419 XRCC6BP1 XRCC6 binding protein 1 A_32_P170406 83660 TLN2 talin 2 A_32_P177024 51119 SBDS Shwachman-Bodian- Diamond syndrome A_32_P217655 645166 LOC645166 lymphocyte-specific protein 1 pseudogene A_32_P2738 26123 TCTN3 tectonic family member 3 A_32_P88965 4921 DDR2 discoidin domain receptor tyrosine kinase 2 GC5 A_23_P13382 4046 LSP1 lymphocyte-specific protein 1 A_23_P138376 22931 RAB18 RAB18, member RAS oncogene family A_23_P140725 9742 IFT140 intraflagellar transport 140 homolog (Chlamydomonas) A_23_P157875 2219 FCN1 ficolin (collagen/fibrinogen domain containing) 1 A_23_P157879 2219 FCN1 ficolin (collagen/fibrinogen domain containing) 1 A_23_P15995 8778 SIGLEC5 sialic acid binding Ig-like lectin 5 A_23_P165219 84106 PRAM1 PML-RARA regulated adaptor molecule 1 A_23_P167256 79960 PHF17 PHD finger protein 17 A_23_P200728 2214 FCGR3A Fc fragment of IgG, low affinity IIIa, receptor (CD16a) A_23_P22444 5199 CFP complement factor properdin A_23_P259561 3109 HLA-DMB major histocompatibility complex, class II, DM beta A_23_P259621 7462 LAT2 linker for activation of T cells family, member 2 A_23_P27994 7305 TYROBP TYRO protein tyrosine kinase binding protein A_23_P31006 3127 HLA-DRB5 major histocompatibility complex, class II, DR beta 5 A_23_P38795 2357 FPR1 formyl peptide receptor 1 A_23_P41765 3659 IRF1 interferon regulatory factor 1 A_23_P48997 9051 PSTPIP1 proline-serine-threonine phosphatase interacting protein 1 A_23_P51534 6846 XCL2 chemokine (C motif) ligand 2 A_23_P85716 2212 FCGR2A Fc fragment of IgG, low affinity IIa, receptor (CD32) A_24_P134229 126282 TNFAIP8L1 tumor necrosis factor, alpha-induced protein 8- like 1 A_24_P192914 120425 AMICA1 adhesion molecule, interacts with CXADR antigen 1 A_24_P283189 929 CD14 CD14 molecule A_24_P343233 3123 HLA-DRB1 major histocompatibility complex, class II, DR beta 1 A_24_P365807 1947 EFNB1 ephrin-B1 GC6 A_23_P100240 1014 CDH16 cadherin 16, KSP-cadherin A_23_P121987 85480 TSLP thymic stromal lymphopoietin A_23_P143331 650 BMP2 bone morphogenetic protein 2 A_23_P147786 9699 RIMS2 regulating synaptic membrane exocytosis 2 A_23_P158096 85301 COL27A1 collagen, type XXVII, alpha 1 A_23_P168259 80328 ULBP2 UL16 binding protein 2 A_23_P252721 10395 DLC1 deleted in liver cancer 1 A_23_P66117 83986 ITFG3 integrin alpha FG-GAP repeat containing 3 A_24_P113295 1175 AP2S1 adaptor-related protein complex 2, sigma 1 subunit A_24_P285163 57645 POGK pogo transposable element with KRAB domain A_24_P334130 2335 FN1 fibronectin 1 A_24_P51909 10815 CPLX1 complexin 1 A_24_P84898 2237 FEN1 flap structure-specific endonuclease 1 A_24_P88870 8706 B3GALNT1 beta-1,3-N- acetylgalactosaminyltransferase 1 (globoside blood group) A_24_P935252 8087 FXR1 fragile X mental retardation, autosomal homolog 1 A_32_P106615 9353 SLIT2 slit homolog 2 (Drosophila) A_32_P121651 57534 MIB1 mindbomb homolog 1 (Drosophila) A_32_P157539 79031 PDCL3 phosducin-like 3 A_32_P200600 5518 PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform A_32_P29806 8738 CRADD CASP2 and RIPK1 domain containing adaptor with death domain A_32_P43717 9413 C9orf61 chromosome 9 open reading frame 61 A_32_P72541 9037 SEMA5A sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A A_32_P84009 146223 CMTM4 CKLF-like MARVEL transmembrane domain containing 4

APPENDIX F

TABLE S6 Weights of sparse CCA Cytokine responses B-cells CD8 CD4 Monocytes Correlation Factors 0.9 0.88 0.87 0.75 Baseline-B-cells −0.9 −0.88 −0.95 −0.75 Baseline-CD4 −0.76 −0.68 −0.79 −0.36 CD8 Naive 0.76 0.72 0.6 0.49 CD8 TDEM −0.67 −0.65 −0.65 −0.49 CD8+CD28− 0.81 0.6 0.7 0.32 CD4 TDEM −0.35 −0.59 −0.56 −0.63 CD4+CD28− 0.19 0.55 0.39 0.65 GC 6 0.52 0.46 0.4 0.26 GC 1 −0.21 −0.39 −0.38 −0.54 NK T −0.4 −0.41 −0.42 −0.18 GC 5 −0.21 −0.32 −0.27 −0.49 GC 3 0.24 0.15 0.24 0.24 Baseline-cd8 −0.42 −0.22 −0.23 −0.02 IL-17 0.38 0 0.16 0 GC 4 0.25 0.18 0.05 0 MPZL2 (A_24_P278552 0 0.08 0.05 0.18 mono 0 −0.01 0 −0.21 IFI30 (A_23_P153745) −0.06 −0.01 −0.05 −0.07 GC 2 0 0 −0.02 −0.17 TGF-a 0 0.05 0.1 0 Th1 −0.15 0 0 0 MCP-3 0 0.06 0.06 0 Th2 0 0.07 0 0 TNF-a 0 −0.02 0 −0.01 chemokines 0 0 0 0 CD8 CenMem 0 0 0 0

APPENDIX G

TABLE S7 Significant differences between CR and CNR Fold- Age: 60-65 yo change Cytokine vs CNR vs response 74+ yo Gender CR p-value q-value p-value q-value p-value q-value Cytokine stimulation response cd4_IFNa_STAT3 4 0 0 0.947037 0.460211 0.153556 0.376565 cd4_IL6_STAT3 6.28 0 0 0.900331 0.443676 0.299048 0.482754 cd4_IL21_STAT3 4.08 0 0 0.829489 0.428303 0.13378 0.376565 cd4_IL10_STAT3 3.8 0 0.000001 0.802164 0.428303 0.340265 0.482754 mono_IFNg_STAT3 1.54 0.000006 0.000025 0.714285 0.420019 0.70903 0.702136 cd8_IL7_STAT1 1.25 0.000015 0.000047 0.135552 0.420019 0.060505 0.291589 mono_IL6_STAT3 3.59 0.000015 0.000047 0.684827 0.420019 0.776648 0.702136 cd8_IFNg_STAT1 2.45 0.000023 0.000064 0.290331 0.420019 0.014834 0.291589 cd8_IL6_STAT3 4.35 0.000034 0.000083 0.24283 0.420019 0.065875 0.291589 cd4_IL6_STAT1 6.81 0.000039 0.000085 0.345614 0.420019 0.310418 0.482754 cd4_IFNa_STAT1 3.16 0.000057 0.000106 0.493856 0.420019 0.166634 0.380318 mono_IFNa_STAT5 1.62 0.000058 0.000106 0.319297 0.420019 0.977993 0.725487 cd4_IL6_STAT5 2.93 0.00007 0.000119 0.53263 0.420019 0.822851 0.708112 mono_IFNa_STAT3 1.75 0.000095 0.000149 0.37638 0.420019 0.995002 0.725487 cd4_IFNg_STAT1 2.22 0.000121 0.000177 0.198227 0.420019 0.092476 0.373417 cd8_IFNa_STAT3 1.78 0.000156 0.000215 0.381077 0.420019 0.066656 0.291589 cd4_IL7_STAT3 1.31 0.00019 0.000241 0.39983 0.420019 0.405702 0.519438 cd8_IL6_STAT1 7.41 0.000197 0.000241 0.340202 0.420019 0.049192 0.291589 cd4_IL21_STAT1 1.83 0.000217 0.000251 0.555918 0.420019 0.108496 0.376565 cd8_IFNa_STAT1 2.79 0.000262 0.000288 0.218327 0.420019 0.137566 0.376565 mono_IFNg_STAT5 1.65 0.000303 0.000318 0.457462 0.420019 0.664712 0.691429 cd8_IL7_STAT3 1.17 0.000936 0.000936 0.730943 0.420019 0.03782 0.291589 mono_IL7_STAT5 1.17 0.001112 0.001063 0.41378 0.420019 0.505697 0.63205 cd20_IFNa_STAT1 2.42 0.001232 0.00113 0.427269 0.420019 0.784512 0.702136 cd4_IL10_STAT1 1.83 0.001462 0.001287 0.840156 0.428303 0.958775 0.725487 cd20_IFNg_STAT1 2.05 0.001556 0.001317 0.618695 0.420019 0.791049 0.702136 cd4_IFNg_STAT3 1.13 0.001933 0.001575 0.514195 0.420019 0.113051 0.376565 mono_IFNa_STAT1 1.71 0.003477 0.002732 0.37889 0.420019 0.839715 0.710969 cd8_IL10_STAT1 1.57 0.003883 0.002947 0.091318 0.420019 0.97801 0.725487 cd8_IFNa_STAT5 2.02 0.004273 0.003134 0.253498 0.420019 0.042724 0.291589 cd8_IL6_STAT5 1.85 0.005126 0.003525 0.493479 0.420019 0.193612 0.423479 cd8_IL21_STAT1 1.51 0.005003 0.003525 0.58113 0.420019 0.133924 0.376565 mono_IFNg_STAT1 1.55 0.009067 0.006046 0.634593 0.420019 0.802532 0.702136 cd20_IL21_STAT1 1.46 0.010978 0.007106 0.330071 0.420019 0.338943 0.482754 mono_IL10_STAT3 1.16 0.028449 0.017863 0.558034 0.420019 0.995066 0.725487 mono_IL21_STAT3 1.11 0.029221 0.017863 0.744283 0.420019 0.315413 0.482754 cd20_IL21_STAT3 1.15 0.042992 0.02557 0.641946 0.420019 0.117569 0.376565 cd8_IL7_STAT5 1.22 0.044731 0.025904 0.069506 0.420019 0.157816 0.376565 cd8_IFNg_STAT5 1.1 0.049497 0.02793 0.682996 0.420019 0.059991 0.291589 cd20_IFNa_STAT3 1.17 0.051587 0.028381 0.337448 0.420019 0.033475 0.291589 cd4_IL7_STAT1 1.19 0.05989 0.032146 0.375581 0.420019 0.629986 0.691429 cd4_IL21_STAT5 1.18 0.080319 0.042084 0.856894 0.428303 0.155441 0.376565 cd4_IFNa_STAT5 1.33 0.092694 0.047439 0.633135 0.420019 0.785958 0.702136 cd8_IL21_STAT5 1.18 0.114836 0.057435 0.718208 0.420019 0.03049 0.291589 cd20_IFNg_STAT3 −1.05 0.14128 0.069091 0.594073 0.420019 0.061708 0.291589 cd4_IFNg_STAT5 1.03 0.154626 0.073974 0.58423 0.420019 0.335123 0.482754 cd20_IL7_STAT1 1.1 0.17748 0.0831 0.471045 0.420019 0.958544 0.725487 cd8_IL10_STAT5 1.13 0.215206 0.098212 0.462871 0.420019 0.684921 0.691429 cd8_IL21_STAT3 1.1 0.21868 0.098212 0.744099 0.420019 0.86352 0.719519 phosphoprotein baseline cd20_Unstimulated_STAT1 −2.57 0.000117 0.000644 0.373293 0.777023 0.619702 0.308798 cd4_Unstimulated_STAT3 −4.2 0.000273 0.000753 0.485768 0.777023 0.062525 0.066939 cd20_Unstimulated_STAT5 −1.11 0.076648 0.070499 0.33538 0.777023 0.841783 0.349551 cd20_Unstimulated_STAT3 −1.11 0.007217 0.009957 0.57577 0.777023 0.024649 0.040941 cd4_Unstimulated_STAT1 −2.15 0.006027 0.009957 0.812278 0.777023 0.010133 0.025246 cd4_Unstimulated_STAT5 −1.05 0.090487 0.071338 0.296912 0.777023 0.00931 0.025246 mono_Unstimulated_STAT1 −1.2 0.019564 0.021594 0.433673 0.777023 0.379235 0.20997 Cell subsets CD8+CD28− −4.21 0.000008 0.000032 0.630348 0.607903 0.005759 0.037864 CD8 TERM DIFF −9.49 0.000032 0.000068 0.389149 0.585539 0.039951 0.058839 EFFECTOR MEMORY CD8 NAIVE 2.14 0.001718 0.002449 0.694365 0.618129 0.032877 0.058839 B CELLS 3.54 0.004612 0.004932 0.817871 0.630998 0.541342 0.237297 CD4 EFFECTOR −5.62 0.012042 0.010302 0.477152 0.585539 0.457482 0.231389 MEMORY CD4 NAIVE 1.48 0.019374 0.013811 0.519746 0.585539 0.111156 0.117433 CD4 TERM DIFF −53.39 0.024124 0.014741 0.556562 0.585539 0.378876 0.217652 EFFECTOR MEMORY NK T CELLS −6.67 0.034716 0.018562 0.163185 0.585539 0.246943 0.202964 CD8 CENTRAL 1.92 0.053228 0.023628 0.549683 0.585539 0.291454 0.208139 MEMORY CD4+CD28− −31.87 0.055239 0.023628 0.319976 0.585539 0.523354 0.237297 GAMMA DELTA −2.58 0.164423 0.063936 0.215857 0.585539 0.044742 0.058839 CELLS CD4 CENTRAL −1.2 0.303572 0.099883 0.751379 0.621106 0.031656 0.058839 MEMORY CD8 EFFECTOR −2.44 0.294813 0.099883 0.3442 0.585539 0.39722 0.217652 MEMORY Gene expression CNTFR 1271 A_23_P9

1.42 0.000002 0.003052 0.468716 0.999497 0.681992 0.999623 CD33 945 A_24_P3

1.55 0.000019 0.014378 0.65498 0.999497 0.569891 0.999623 CCL5 6352 A_23_P1

−8.16 0.000025 0.014378 0.852489 0.999497 0.771658 0.999623 UBE2I 7329 A_23_P1

1.59 0.001915 0.036104 0.935523 0.999497 0.9852 0.999623 NAE1 8883 A_23_P7

−1.72 0.000889 0.036104 0.528884 0.999497 0.609482 0.999623 F5 2153 A_32_P4

1.48 0.001425 0.036104 0.401274 0.999497 0.503965 0.999623 PGM5 5239 A_24_P1

1.41 0.001015 0.036104 0.327167 0.999497 0.051766 0.999623 CRYAB 1410 A_24_P2

1.71 0.001353 0.036104 0.870361 0.999497 0.77123 0.999623 FOS 2353 A_23_P1

1.66 0.001921 0.036104 0.630412 0.999497 0.655547 0.999623 NUPR1 26471 A_24_P2

1.72 0.001261 0.036104 0.544316 0.999497 0.86663 0.999623 COL6A2 1292 A_23_P2

2.12 0.001914 0.036104 0.443149 0.999497 0.685136 0.999623 ACTN4 81 A_23_P3

2 0.001969 0.036104 0.477143 0.999497 0.541507 0.999623 NOG 9241 A_23_P3

1.9 0.000533 0.036104 0.851653 0.999497 0.264467 0.999623 CAPN10 11132 A_23_P3

1.93 0.001745 0.036104 0.113584 0.999497 0.295294 0.999623 HDAC5 10014 A_23_P2

1.85 0.001396 0.036104 0.755511 0.999497 0.244218 0.999623 CUTA 51596 A_23_P2

1.6 0.000807 0.036104 0.612211 0.999497 0.241352 0.999623 TGFB1I1 7041 A_23_P1

1.99 0.000809 0.036104 0.822061 0.999497 0.246581 0.999623 SOD1 6647 A_23_P1

1.62 0.001546 0.036104 0.662823 0.999497 0.535483 0.999623 NRP2 8828 A_24_P5

1.72 0.001623 0.036104 0.952429 0.999497 0.133472 0.999623 FOLR1 2348 A_23_P5

1.93 0.000554 0.036104 0.892212 0.999497 0.193482 0.999623 MKNK2 2872 A_24_P9

1.74 0.001284 0.036104 0.769347 0.999497 0.224105 0.999623 RAMP3 10268 A_23_P1

1.86 0.000877 0.036104 0.846338 0.999497 0.58297 0.999623 IGF1R 3480 A_23_P2

1.67 0.000913 0.036104 0.644569 0.999497 0.996777 0.999623 FXYD5 53827 A_24_P1

1.65 0.000561 0.036104 0.387527 0.999497 0.632614 0.999623 ZNF346 23567 A_23_P4

1.55 0.001565 0.036104 0.956026 0.999497 0.621718 0.999623 CIAPIN1 57019 A_23_P8

1.4 0.000741 0.036104 0.91067 0.999497 0.828879 0.999623 DAB2 1601 A_23_P2

1.65 0.001499 0.036104 0.734123 0.999497 0.216778 0.999623 CEACAM1 634 A_24_P3

−2.09 0.00171 0.036104 0.818157 0.999497 0.367309 0.999623 LSP1 4046 A_32_P1

1.38 0.001183 0.036104 0.858935 0.999497 0.539176 0.999623 CCL3 6348 A_23_P3

1.47 0.00082 0.036104 0.753777 0.999497 0.835003 0.999623 HIC1 3090 A_23_P1

1.39 0.001829 0.036104 0.756911 0.999497 0.266203 0.999623 RICTOR 253260 A_32_P1

−3.17 0.000688 0.036104 0.892103 0.999497 0.896246 0.999623 LOC731884 731884 A_32_P1

−1.52 0.000346 0.036104 0.546338 0.999497 0.970792 0.999623 C11orf82 220042 A_23_P4

−1.83 0.000382 0.036104 0.969107 0.999497 0.454269 0.999623 ADH5 128 A_24_P2

−1.83 0.000181 0.036104 0.991188 0.999497 0.537529 0.999623 LRP12 29967 A_23_P8

−2.5 0.001269 0.036104 0.615746 0.999497 0.632577 0.999623 RIMS4 140730 A_24_P3

−1.89 0.000957 0.036104 0.922956 0.999497 0.49328 0.999623 BMI1 648 A_23_P3

−5.23 0.001737 0.036104 0.47677 0.999497 0.588522 0.999623 FNBP1L 54874 A_23_P4

−2.18 0.000321 0.036104 0.592882 0.999497 0.4161 0.999623 KCNMA1 3778 A_32_P1

1.28 0.001967 0.036104 0.735474 0.999497 0.411288 0.999623 SCRN1 9805 A_23_P3

1.51 0.001041 0.036104 0.413517 0.999497 0.643565 0.999623 NRTN 4902 A_23_P9

2.19 0.001956 0.036104 0.480441 0.999497 0.274495 0.999623 GZMH 2999 A_23_P1

−20.32 0.000372 0.036104 0.48478 0.999497 0.732471 0.999623 MAP4K2 5871 A_24_P2

2.04 0.00125 0.036104 0.95861 0.999497 0.783462 0.999623 PCDHB11 56125 A_23_P1

1.62 0.001861 0.036104 0.644295 0.999497 0.471202 0.999623 HCG18 414777 A_32_P1

1.93 0.001725 0.036104 0.718093 0.999497 0.310781 0.999623 FSCN1 6624 A_23_P1

2.08 0.000886 0.036104 0.959932 0.999497 0.756668 0.999623 MUC5AC 4586 A_24_P7

1.91 0.000211 0.036104 0.565104 0.999497 0.972326 0.999623 NINJ1 4814 A_23_P1

1.97 0.001275 0.036104 0.954106 0.999497 0.255055 0.999623 PSMD4 5710 A_23_P1

1.62 0.00196 0.036104 0.662586 0.999497 0.272692 0.999623 CLN3 1201 A_24_P1

1.62 0.001455 0.036104 0.84645 0.999497 0.546117 0.999623 PYCARD 29108 A_23_P2

1.46 0.001903 0.036104 0.995796 0.999497 0.50099 0.999623 UTP14A 10813 A_24_P1

−1.96 0.001041 0.036104 0.973791 0.999497 0.634985 0.999623 RPS3A 6189 A_32_P1

−1.64 0.001684 0.036104 0.741683 0.999497 0.677281 0.999623 TYMP 1890 A_23_P9

1.88 0.000299 0.036104 0.963687 0.999497 0.535271 0.999623 PLD2 5338 A_23_P4

1.43 0.001952 0.036104 0.59288 0.999497 0.9276 0.999623 FGFR1 2260 A_24_P4

1.75 0.001282 0.036104 0.510266 0.999497 0.702185 0.999623 TGM2 7052 A_24_P9

1.44 0.001857 0.036104 0.406185 0.999497 0.678772 0.999623 AP2A1 160 A_23_P4

1.54 0.001371 0.036104 0.657812 0.999497 0.805783 0.999623 C16orf5 29965 A_23_P1

1.45 0.000499 0.036104 0.79947 0.999497 0.456699 0.999623 AREG 374 A_23_P2

1.6 0.00181 0.036104 0.425941 0.999497 0.55855 0.999623 CHST10 9486 A_23_P1

1.56 0.000695 0.036104 0.524686 0.999497 0.752694 0.999623 LOC91316 91316 A_24_P9

1.35 0.000436 0.036104 0.512559 0.999497 0.65309 0.999623 ARHGEF11 9826 A_23_P4

1.58 0.001814 0.036104 0.829165 0.999497 0.794249 0.999623 IL3RA 3563 A_23_P2

1.7 0.000099 0.036104 0.95942 0.999497 0.34963 0.999623 YKT6 10652 A_24_P3

1.72 0.000851 0.036104 0.917946 0.999497 0.584568 0.999623 PEX5 5830 A_24_P3

1.71 0.001585 0.036104 0.832499 0.999497 0.935308 0.999623 RAB5B 5869 A_23_P1

1.44 0.000215 0.036104 0.605261 0.999497 0.777266 0.999623 TCTA 6988 A_24_P1

1.8 0.000417 0.036104 0.272418 0.999497 0.520236 0.999623 TRAP1 10131 A_23_P3

1.44 0.001417 0.036104 0.249931 0.999497 0.377573 0.999623 KYNU 8942 A_23_P5

1.42 0.001445 0.036104 0.582003 0.999497 0.598451 0.999623 FN1 2335 A_32_P9

1.81 0.000524 0.036104 0.77332 0.999497 0.2 0.999623 TRIP10 9322 A_23_P5

1.78 0.00032 0.036104 0.476946 0.999497 0.552793 0.999623 PIN1 5300 A_23_P6

1.67 0.001732 0.036104 0.8874 0.999497 0.272875 0.999623 RIN2 54453 A_23_P9

1.64 0.000727 0.036104 0.689161 0.999497 0.820036 0.999623 BSCL2 26580 A_24_P2

1.72 0.00045 0.036104 0.692057 0.999497 0.61986 0.999623 PCDHA1 56147 A_24_P1

1.62 0.000977 0.036104 0.526039 0.999497 0.447015 0.999623 ZNF346 23567 A_23_P4

1.58 0.000724 0.036104 0.490382 0.999497 0.592862 0.999623 CCND1 595 A_24_P1

1.75 0.001864 0.036104 0.703558 0.999497 0.411183 0.999623 EPO 2056 A_23_P1

1.76 0.000322 0.036104 0.959527 0.999497 0.840031 0.999623 FAT1 2195 A_23_P6

1.39 0.000235 0.036104 0.646189 0.999497 0.852769 0.999623 DBNL 28988 A_23_P1

1.87 0.000995 0.036104 0.74013 0.999497 0.345923 0.999623 PDLIM7 9260 A_23_P1

1.58 0.001505 0.036104 0.818648 0.999497 0.993117 0.999623 SNCG 6623 A_23_P2

1.66 0.001516 0.036104 0.519845 0.999497 0.314046 0.999623 PTPRF 5792 A_23_P2

2.14 0.000486 0.036104 0.898652 0.999497 0.867885 0.999623 FOXO1 2308 A_24_P2

1.43 0.001 0.036104 0.289655 0.999497 0.979632 0.999623 SNAPIN 23557 A_23_P1

1.32 0.000764 0.036104 0.738372 0.999497 0.441884 0.999623 BAALC 79870 A_23_P1

1.61 0.001112 0.036104 0.338482 0.999497 0.795973 0.999623 GSS 2937 A_23_P2

1.36 0.001469 0.036104 0.798475 0.999497 0.45919 0.999623 ADAL 161823 A_32_P2

1.5 0.001468 0.036104 0.931525 0.999497 0.881205 0.999623 MLF1 4291 A_23_P1

1.46 0.000909 0.036104 0.453641 0.999497 0.677062 0.999623 FOXO4 4303 A_24_P3

1.27 0.000497 0.036104 0.56281 0.999497 0.274221 0.999623 EMILIN1 11117 A_32_P7

1.43 0.000714 0.036104 0.986821 0.999497 0.646397 0.999623 C1QTNF1 114897 A_23_P3

1.54 0.001265 0.036104 0.881114 0.999497 0.746563 0.999623 CD99L2 83692 A_23_P2

1.71 0.004014 0.036799 0.523831 0.999497 0.828093 0.999623 CLSTN3 9746 A_23_P5

1.47 0.003655 0.036799 0.552344 0.999497 0.995555 0.999623 PI4KB 5298 A_23_P3

1.76 0.003335 0.036799 0.678786 0.999497 0.727324 0.999623 LAMA5 3911 A_23_P1

2.03 0.003997 0.036799 0.943309 0.999497 0.531834 0.999623 FEZ2 9637 A_23_P3

1.24 0.002046 0.036799 0.626235 0.999497 0.372874 0.999623 PPP1R15A 23645 A_23_P9

1.72 0.003598 0.036799 0.672479 0.999497 0.386734 0.999623 PPIG 9360 A_23_P1

−1.81 0.00368 0.036799 0.584021 0.999497 0.704251 0.999623 NKG7 4818 A_23_P1

−8.38 0.002739 0.036799 0.96245 0.999497 0.65534 0.999623 RAB3B 5865 A_24_P9

−1.34 0.002854 0.036799 0.977899 0.999497 0.311996 0.999623 MAP4K4 9448 A_23_P9

−1.63 0.003976 0.036799 0.708133 0.999497 0.50406 0.999623 NOS3 4846 A_23_P7

1.66 0.002663 0.036799 0.64946 0.999497 0.911586 0.999623 TCL1A 8115 A_23_P3

3.84 0.003301 0.036799 0.250558 0.999497 0.449763 0.999623 LTBP2 4053 A_23_P2

1.66 0.00387 0.036799 0.502699 0.999497 0.480426 0.999623 MGMT 4255 A_23_P1

1.62 0.002836 0.036799 0.833298 0.999497 0.295631 0.999623 PARVB 29780 A_23_P4

1.57 0.002688 0.036799 0.348734 0.999497 0.503429 0.999623 ERBB2 2064 A_23_P8

2.17 0.002514 0.036799 0.750799 0.999497 0.790942 0.999623 RRAD 6236 A_23_P8

2.06 0.003003 0.036799 0.685343 0.999497 0.202877 0.999623 ACIN1 22985 A_23_P1

1.75 0.002299 0.036799 0.917116 0.999497 0.446935 0.999623 FANCC 2176 A_23_P3

1.5 0.002675 0.036799 0.903823 0.999497 0.727957 0.999623 RSPH3 83861 A_23_P5

1.39 0.002969 0.036799 0.564778 0.999497 0.330631 0.999623 MYC 4609 A_24_P3

1.62 0.003476 0.036799 0.72846 0.999497 0.515281 0.999623 HDAC5 10014 A_24_P1

1.64 0.00221 0.036799 0.787224 0.999497 0.351233 0.999623 PRKRA 8575 A_23_P9

−2.37 0.002484 0.036799 0.819817 0.999497 0.404809 0.999623 CD276 80381 A_23_P5

1.56 0.00329 0.036799 0.407954 0.999497 0.530047 0.999623 ITGB8 3696 A_24_P7

−3.02 0.003897 0.036799 0.766779 0.999497 0.530018 0.999623 DDR1 780 A_24_P3

1.65 0.003704 0.036799 0.831862 0.999497 0.19632 0.999623 DCTN3 11258 A_23_P1

1.39 0.003757 0.036799 0.734811 0.999497 0.13659 0.999623 CSNK1E 1454 A_24_P9

1.49 0.002487 0.036799 0.842292 0.999497 0.311868 0.999623 ADRA1B 147 A_23_P3

1.77 0.002217 0.036799 0.434475 0.999497 0.939526 0.999623 LGALS12 85329 A_23_P1

1.9 0.002282 0.036799 0.50909 0.999497 0.705245 0.999623 HLA-C 3107 A_23_P7

1.88 0.00371 0.036799 0.691174 0.999497 0.597814 0.999623 RALA 5898 A_24_P1

−1.44 0.003584 0.036799 0.711675 0.999497 0.240291 0.999623 C1QTNF4 114900 A_23_P5

1.53 0.00299 0.036799 0.70973 0.999497 0.560858 0.999623 HSPA8 3312 A_32_P1

−2.16 0.003663 0.036799 0.893335 0.999497 0.511234 0.999623 IFNA4 3441 A_24_P4

−2.8 0.003451 0.036799 0.638658 0.999497 0.312166 0.999623 RAB18 22931 A_24_P1

−1.67 0.003088 0.036799 0.567201 0.999497 0.417807 0.999623 LRP12 29967 A_24_P4

−2.71 0.00382 0.036799 0.939237 0.999497 0.323012 0.999623 CD320 51293 A_23_P1

1.66 0.003495 0.036799 0.933906 0.999497 0.526329 0.999623 NEDD4L 23327 A_23_P2

1.29 0.003033 0.036799 0.387082 0.999497 0.016414 0.999623 GH1 2688 A_23_P2

−1.87 0.002357 0.036799 0.478376 0.999497 0.26117 0.999623 PSMG2 56984 A_24_P3

−1.66 0.002488 0.036799 0.448467 0.999497 0.467237 0.999623 NLGN1 22871 A_23_P1

−1.44 0.003168 0.036799 0.926995 0.999497 0.723127 0.999623 LIN7C 55327 A_24_P9

−3.08 0.002742 0.036799 0.310595 0.999497 0.185406 0.999623 CXADR 1525 A_24_P3

−1.93 0.003767 0.036799 0.895248 0.999497 0.420753 0.999623 HLA-C 3107 A_32_P1

−1.95 0.003887 0.036799 0.944433 0.999497 0.981696 0.999623 MUC5AC 4586 A_24_P5

−2.44 0.002238 0.036799 0.456842 0.999497 0.190606 0.999623 COL14A1 7373 A_24_P2

−2.69 0.003725 0.036799 0.873276 0.999497 0.607016 0.999623 5-Sep 5413 A_23_P1

1.73 0.002616 0.036799 0.661674 0.999497 0.262184 0.999623 SKAP2 8935 A_24_P8

1.46 0.002665 0.036799 0.171854 0.999497 0.504189 0.999623 BCL2L12 83596 A_23_P5

1.61 0.003724 0.036799 0.384718 0.999497 0.243259 0.999623 FXYD5 53827 A_23_P1

1.83 0.003836 0.036799 0.379437 0.999497 0.559681 0.999623 TMX1 81542 A_23_P7

1.39 0.002725 0.036799 0.673962 0.999497 0.601861 0.999623 IL3RA 3563 A_32_P2

1.93 0.003195 0.036799 0.619472 0.999497 0.483508 0.999623 PKD1 5310 A_24_P4

1.53 0.003118 0.036799 0.562036 0.999497 0.723101 0.999623 CX3CL1 6376 A_23_P3

2.01 0.003135 0.036799 0.972373 0.999497 0.800236 0.999623 BMF 90427 A_23_P3

1.76 0.00305 0.036799 0.854947 0.999497 0.599953 0.999623 NFATC1 4772 A_23_P3

1.96 0.003188 0.036799 0.744964 0.999497 0.38305 0.999623 KEL 3792 A_23_P2

1.47 0.002375 0.036799 0.521584 0.999497 0.723356 0.999623 CTSD 1509 A_23_P5

2.11 0.00327 0.036799 0.689915 0.999497 0.102454 0.999623 LOC644297 644297 A_23_P1

1.74 0.002326 0.036799 0.966498 0.999497 0.123516 0.999623 EMD 2010 A_23_P8

2.27 0.003097 0.036799 0.973726 0.999497 0.271842 0.999623 CD1A 909 A_23_P4

1.49 0.002533 0.036799 0.824906 0.999497 0.720479 0.999623 GZMA 3001 A_23_P1

−2.87 0.003841 0.036799 0.484362 0.999497 0.997193 0.999623 UCP2 7351 A_23_P4

1.96 0.002975 0.036799 0.739123 0.999497 0.455132 0.999623 WFS1 7466 A_23_P1

1.68 0.002796 0.036799 0.803433 0.999497 0.543886 0.999623 RAB22A 57403 A_32_P1

1.49 0.003676 0.036799 0.943042 0.999497 0.874004 0.999623 PCDHB2 56133 A_24_P2

1.35 0.00383 0.036799 0.993183 0.999497 0.174231 0.999623 BECN1 8678 A_23_P4

−1.27 0.002554 0.036799 0.580946 0.999497 0.957391 0.999623 PRDX2 7001 A_24_P1

1.66 0.003664 0.036799 0.452472 0.999497 0.979373 0.999623 TTRAP 51567 A_23_P8

−2.25 0.003941 0.036799 0.751661 0.999497 0.841923 0.999623 MRPS30 10884 A_23_P2

−1.33 0.002741 0.036799 0.57551 0.999497 0.400199 0.999623 IL17RD 54756 A_32_P1

−1.88 0.002724 0.036799 0.927843 0.999497 0.664638 0.999623 AIF1 199 A_23_P2

1.94 0.004012 0.036799 0.461864 0.999497 0.348074 0.999623 RNF216 54476 A_24_P4

−1.6 0.002874 0.036799 0.780076 0.999497 0.8195 0.999623 HMGB1 3146 A_23_P9

−2.4 0.002061 0.036799 0.561096 0.999497 0.275322 0.999623 BSG 682 A_32_P2

1.71 0.003834 0.036799 0.971549 0.999497 0.157925 0.999623 ERBB3 2065 A_23_P3

1.64 0.002964 0.036799 0.997041 0.999497 0.505466 0.999623 TNFRSF10B 8795 A_23_P1

1.47 0.003361 0.036799 0.72306 0.999497 0.811524 0.999623 PLD1 5337 A_23_P3

1.49 0.002554 0.036799 0.264221 0.999497 0.791086 0.999623 MYST4 23522 A_23_P3

1.57 0.002953 0.036799 0.942193 0.999497 0.829364 0.999623 COL16A1 1307 A_23_P1

1.39 0.003366 0.036799 0.120822 0.999497 0.934672 0.999623 BMP1 649 A_23_P3

1.86 0.003944 0.036799 0.63638 0.999497 0.629346 0.999623 RAB3D 9545 A_23_P4

1.39 0.003287 0.036799 0.446421 0.999497 0.2315 0.999623 DCHS1 8642 A_23_P9

1.82 0.002777 0.036799 0.650747 0.999497 0.391191 0.999623 AQP3 360 A_23_P1

1.53 0.002361 0.036799 0.643996 0.999497 0.807047 0.999623 B3GNTL1 146712 A_24_P1

1.71 0.002961 0.036799 0.83054 0.999497 0.598684 0.999623 COL24A1 255631 A_23_P7

1.81 0.003256 0.036799 0.933385 0.999497 0.785361 0.999623 LAMA1 284217 A_23_P1

1.82 0.002498 0.036799 0.546325 0.999497 0.524802 0.999623 HMGB3 3149 A_23_P2

1.42 0.002816 0.036799 0.61878 0.999497 0.89304 0.999623 IGSF8 93185 A_23_P1

1.68 0.00376 0.036799 0.999039 0.999497 0.719943 0.999623 MMP12 4321 A_23_P3

1.29 0.002657 0.036799 0.592962 0.999497 0.921481 0.999623 HSPA8 3312 A_24_P2

−1.98 0.003382 0.036799 0.119957 0.999497 0.901493 0.999623 ARVCF 421 A_23_P1

1.59 0.002613 0.036799 0.759477 0.999497 0.366938 0.999623 PVR 5817 A_23_P1

1.4 0.003357 0.036799 0.491225 0.999497 0.474115 0.999623 HIF1A 3091 A_23_P4

−1.71 0.004371 0.036858 0.92804 0.999497 0.387877 0.999623 TRAF1 7185 A_23_P2

1.99 0.004122 0.036858 0.978755 0.999497 0.699893 0.999623 SECTM1 6398 A_24_P3

2.07 0.004322 0.036858 0.821937 0.999497 0.82145 0.999623 PRKCD 5580 A_23_P1

1.47 0.004481 0.036858 0.914646 0.999497 0.799097 0.999623 RAB5C 5878 A_23_P1

1.49 0.004129 0.036858 0.503106 0.999497 0.673735 0.999623 SERPINB2 5055 A_23_P1

1.88 0.004089 0.036858 0.428911 0.999497 0.152952 0.999623 VPREB3 29802 A_23_P1

1.45 0.004403 0.036858 0.980636 0.999497 0.644839 0.999623 TOLLIP 54472 A_24_P9

−2.02 0.004345 0.036858 0.688941 0.999497 0.146524 0.999623 MIB1 57534 A_24_P9

−1.49 0.00443 0.036858 0.540753 0.999497 0.639846 0.999623 NEIL3 55247 A_23_P1

−4.87 0.004452 0.036858 0.608058 0.999497 0.360265 0.999623 MLXIPL 51085 A_23_P1

1.62 0.004438 0.036858 0.447741 0.999497 0.220519 0.999623 GYPA 2993 A_23_P4

−1.56 0.004533 0.036858 0.923595 0.999497 0.225265 0.999623 PACSIN3 29763 A_24_P3

1.69 0.004502 0.036858 0.847646 0.999497 0.868742 0.999623 BAT2 7916 A_24_P6

2.13 0.004534 0.036858 0.612267 0.999497 0.871152 0.999623 EIF5A 1984 A_24_P3

1.46 0.004298 0.036858 0.272048 0.999497 0.639329 0.999623 RIN1 9610 A_23_P6

2.09 0.004233 0.036858 0.606987 0.999497 0.933581 0.999623 CPXM1 56265 A_23_P6

1.76 0.004096 0.036858 0.420615 0.999497 0.996511 0.999623 OXSR1 9943 A_24_P2

1.77 0.004221 0.036858 0.876339 0.999497 0.879169 0.999623 THBS4 7060 A_24_P2

1.41 0.004154 0.036858 0.881901 0.999497 0.417252 0.999623 DOK1 1796 A_23_P5

1.29 0.004495 0.036858 0.978146 0.999497 0.650775 0.999623 FLNA 2316 A_23_P9

1.41 0.00425 0.036858 0.596631 0.999497 0.761419 0.999623 MDM2 4193 A_23_P3

1.4 0.004394 0.036858 0.764841 0.999497 0.521728 0.999623 NCAM1 4684 A_23_P1

1.47 0.004492 0.036858 0.542844 0.999497 0.155061 0.999623 MAPK13 5603 A_24_P4

1.52 0.004418 0.036858 0.852344 0.999497 0.867762 0.999623 CD8A 925 A_32_P1

−4.02 0.004597 0.036918 0.582391 0.999497 0.425898 0.999623 FIS1 51024 A_24_P2

1.38 0.004627 0.036918 0.625394 0.999497 0.756806 0.999623 RAB13 5872 A_23_P4

−1.89 0.004574 0.036918 0.738182 0.999497 0.778696 0.999623 PDLIM7 9260 A_24_P4

1.38 0.004608 0.036918 0.081496 0.999497 0.470102 0.999623 BGLAP 632 A_24_P3

1.79 0.004673 0.036962 0.879465 0.999497 0.252697 0.999623 DDIT4 54541 A_23_P1

1.48 0.004676 0.036962 0.988634 0.999497 0.783134 0.999623 HRAS 3265 A_23_P9

1.44 0.004932 0.036987 0.329159 0.999497 0.667962 0.999623 NAIP 4671 A_23_P1

−2.54 0.004925 0.036987 0.75741 0.999497 0.648142 0.999623 C7 730 A_23_P2

−2.26 0.004791 0.036987 0.790559 0.999497 0.249087 0.999623 TRGV5 6978 A_24_P9

−2.17 0.004796 0.036987 0.932939 0.999497 0.694945 0.999623 HAPLN3 145864 A_23_P1

1.44 0.004737 0.036987 0.337781 0.999497 0.514733 0.999623 HDAC4 9759 A_24_P3

1.58 0.00483 0.036987 0.924326 0.999497 0.332864 0.999623 FN1 2335 A_24_P8

1.86 0.004957 0.036987 0.330315 0.999497 0.353643 0.999623 P2RX7 5027 A_24_P3

1.6 0.004958 0.036987 0.491895 0.999497 0.473055 0.999623 DEFB4 1673 A_23_P1

−1.54 0.004745 0.036987 0.642515 0.999497 0.472583 0.999623 LSM14B 149986 A_23_P3

1.52 0.004897 0.036987 0.57233 0.999497 0.670692 0.999623 TCTA 6988 A_23_P5

1.79 0.004727 0.036987 0.92342 0.999497 0.754902 0.999623 NAB2 4665 A_23_P3

1.72 0.004896 0.036987 0.188646 0.999497 0.784659 0.999623 PODXL2 50512 A_23_P1

1.38 0.004862 0.036987 0.458616 0.999497 0.688154 0.999623 GDF6 392255 A_32_P1

−2.06 0.005064 0.037134 0.945682 0.999497 0.567596 0.999623 SCD5 79966 A_24_P4

−1.62 0.005043 0.037134 0.845392 0.999497 0.33532 0.999623 ITGA11 22801 A_23_P2

1.95 0.005028 0.037134 0.972503 0.999497 0.807434 0.999623 CD38 952 A_23_P1

1.55 0.00501 0.037134 0.468403 0.999497 0.769658 0.999623 N-PAC 84656 A_23_P2

1.55 0.00517 0.037756 0.19692 0.999497 0.622897 0.999623 CLDN14 23562 A_23_P9

2.03 0.005196 0.037781 0.831003 0.999497 0.563221 0.999623 SDF2L1 23753 A_23_P6

1.79 0.005308 0.038434 0.840802 0.999497 0.951897 0.999623 HOXB7 3217 A_23_P4

1.62 0.005445 0.038772 0.89319 0.999497 0.47444 0.999623 HSPA5 3309 A_24_P9

1.47 0.005433 0.038772 0.42492 0.999497 0.453205 0.999623 PDGFC 56034 A_23_P5

−1.64 0.005383 0.038772 0.92027 0.999497 0.698472 0.999623 TNFSF13 8741 A_23_P1

1.43 0.005431 0.038772 0.119195 0.999497 0.94806 0.999623 ATP6V1H 51606 A_24_P3

−2.05 0.005562 0.039126 0.885499 0.999497 0.39461 0.999623 BAX 581 A_23_P2

1.42 0.005542 0.039126 0.168214 0.999497 0.648696 0.999623 NEIL2 252969 A_32_P1

1.43 0.005523 0.039126 0.239915 0.999497 0.303618 0.999623 EPN2 22905 A_23_P8

1.6 0.005599 0.039227 0.403423 0.999497 0.729579 0.999623 CXCL14 9547 A_23_P2

1.27 0.005651 0.039425 0.959343 0.999497 0.967797 0.999623 BOC 91653 A_23_P2

1.49 0.005835 0.039662 0.962864 0.999497 0.925063 0.999623 AKAP11 11215 A_23_P2

−1.85 0.00588 0.039662 0.851873 0.999497 0.590879 0.999623 3-Sep 55964 A_23_P5

1.56 0.005927 0.039662 0.768511 0.999497 0.969072 0.999623 N-PAC 84656 A_32_P7

1.84 0.006007 0.039662 0.81878 0.999497 0.609 0.999623 SEMA3C 10512 A_23_P2

−1.79 0.00588 0.039662 0.797983 0.999497 0.995553 0.999623 C3orf38 285237 A_23_P4

−1.99 0.005996 0.039662 0.086769 0.999497 0.901564 0.999623 PRSS2 5645 A_23_P3

1.55 0.005948 0.039662 0.710419 0.999497 0.131909 0.999623 WNK1 65125 A_24_P7

−1.81 0.005813 0.039662 0.265821 0.999497 0.292153 0.999623 DOCK7 85440 A_23_P3

−1.73 0.00582 0.039662 0.580693 0.999497 0.140506 0.999623 IGHV1-69 28461 A_24_P3

1.71 0.005994 0.039662 0.818702 0.999497 0.768258 0.999623 ASB1 51665 A_23_P1

1.68 0.005896 0.039662 0.63158 0.999497 0.474956 0.999623 AP1B1 162 A_23_P6

1.56 0.005872 0.039662 0.593906 0.999497 0.053772 0.999623 PRKCQ 5588 A_23_P1

1.25 0.005884 0.039662 0.268524 0.999497 0.118193 0.999623 RAE1 8480 A_23_P3

1.27 0.006 0.039662 0.574388 0.999497 0.441716 0.999623 CFL1 1072 A_23_P3

1.57 0.006039 0.039725 0.834753 0.999497 0.423084 0.999623 CISH 1154 A_24_P9

1.75 0.006192 0.039811 0.957882 0.999497 0.838468 0.999623 NFKBIL1 4795 A_23_P1

2.06 0.006091 0.039811 0.666764 0.999497 0.296183 0.999623 BMP1 649 A_24_P6

1.48 0.00623 0.039811 0.765526 0.999497 0.075354 0.999623 TRIB3 57761 A_24_P3

1.87 0.006237 0.039811 0.566477 0.999497 0.47545 0.999623 PLAGL2 5326 A_23_P6

−1.68 0.006188 0.039811 0.79153 0.999497 0.351673 0.999623 CDH16 1014 A_23_P1

1.58 0.006166 0.039811 0.613212 0.999497 0.481024 0.999623 HTT 3064 A_23_P2

1.72 0.006125 0.039811 0.759241 0.999497 0.135237 0.999623 CROP 51747 A_23_P2

1.32 0.0062 0.039811 0.233464 0.999497 0.201247 0.999623 RP11-138L21.1 389722 A_24_P6

1.28 0.00632 0.039896 0.569351 0.999497 0.38752 0.999623 INHBC 3626 A_24_P1

−2.23 0.006301 0.039896 0.239035 0.999497 0.254386 0.999623 TNXB 7148 A_23_P1

1.8 0.006276 0.039896 0.24883 0.999497 0.190948 0.999623 GLT25D2 23127 A_24_P6

1.25 0.006343 0.039897 0.665854 0.999497 0.624613 0.999623 CD163L1 283316 A_23_P6

1.79 0.006394 0.040067 0.597613 0.999497 0.974297 0.999623 PEX5 5830 A_23_P4

1.57 0.006757 0.040193 0.55322 0.999497 0.393006 0.999623 TP53 7157 A_23_P2

1.45 0.006593 0.040193 0.329323 0.999497 0.229693 0.999623 EGF 1950 A_23_P1

1.54 0.006706 0.040193 0.380675 0.999497 0.847549 0.999623 WDR59 79726 A_23_P2

1.46 0.006684 0.040193 0.643522 0.999497 0.658962 0.999623 STXBP2 6813 A_24_P9

1.53 0.006513 0.040193 0.997036 0.999497 0.248488 0.999623 SLIT2 9353 A_23_P1

1.78 0.006488 0.040193 0.411598 0.999497 0.557526 0.999623 GPR98 84059 A_23_P1

−1.54 0.006643 0.040193 0.388514 0.999497 0.809156 0.999623 HDAC4 9759 A_23_P2

−1.33 0.006618 0.040193 0.060507 0.999497 0.79865 0.999623 ICAM3 3385 A_23_P1

1.73 0.006764 0.040193 0.503806 0.999497 0.315636 0.999623 LMLN 89782 A_23_P4

1.46 0.006627 0.040193 0.514015 0.999497 0.949942 0.999623 TNFRSF6B 8771 A_23_P2

1.65 0.006541 0.040193 0.474909 0.999497 0.401812 0.999623 ARF6 382 A_24_P4

−2.6 0.00665 0.040193 0.295516 0.999497 0.157962 0.999623 JUB 84962 A_23_P5

−1.4 0.006721 0.040193 0.665982 0.999497 0.635921 0.999623 ELMOD3 84173 A_23_P1

1.47 0.006751 0.040193 0.76838 0.999497 0.690694 0.999623 CD59 966 A_24_P6

1.89 0.006571 0.040193 0.178875 0.999497 0.711986 0.999623 DLG1 1739 A_24_P1

−1.84 0.006882 0.040756 0.858759 0.999497 0.640739 0.999623 COL14A1 7373 A_32_P8

1.76 0.007048 0.040877 0.599642 0.999497 0.416598 0.999623 CAV3 859 A_24_P2

−1.31 0.007088 0.040877 0.305798 0.999497 0.317434 0.999623 TGM2 7052 A_32_P8

1.42 0.007119 0.040877 0.831014 0.999497 0.131657 0.999623 TNIP1 10318 A_23_P3

1.53 0.007087 0.040877 0.947415 0.999497 0.046481 0.999623 MEN1 4221 A_23_P7

1.68 0.007056 0.040877 0.911128 0.999497 0.159982 0.999623 ARRB2 409 A_23_P1

1.59 0.007077 0.040877 0.779283 0.999497 0.615331 0.999623 CTNND2 1501 A_23_P1

1.56 0.00707 0.040877 0.759584 0.999497 0.73204 0.999623 THBS2 7058 A_23_P6

−1.48 0.007122 0.040877 0.533028 0.999497 0.934161 0.999623 PBX2 5089 A_32_P1

1.25 0.00714 0.040877 0.428924 0.999497 0.430511 0.999623 CSNK2B 1460 A_24_P8

1.29 0.007037 0.040877 0.538916 0.999497 0.391645 0.999623 CLDN23 137075 A_23_P1

1.56 0.007175 0.040946 0.308815 0.999497 0.041708 0.999623 THBS1 7057 A_23_P2

1.44 0.007267 0.040951 0.561238 0.999497 0.402662 0.999623 DCBLD2 131566 A_24_P1

−1.63 0.007231 0.040951 0.684511 0.999497 0.780267 0.999623 CBX4 8535 A_23_P8

1.65 0.007227 0.040951 0.721296 0.999497 0.873026 0.999623 ISG20L2 81875 A_23_P1

1.39 0.007271 0.040951 0.949767 0.999497 0.722942 0.999623 LY75 4065 A_23_P3

−2.1 0.007393 0.0411 0.280371 0.999497 0.554946 0.999623 ARHGDIA 396 A_24_P3

1.65 0.007441 0.0411 0.381574 0.999497 0.805743 0.999623 CCL16 6360 A_23_P2

1.44 0.007347 0.0411 0.660933 0.999497 0.812475 0.999623 EMILIN2 84034 A_23_P2

1.43 0.007433 0.0411 0.873004 0.999497 0.924728 0.999623 MAF 4094 A_23_P3

1.62 0.007349 0.0411 0.280531 0.999497 0.933361 0.999623 MYBPH 4608 A_23_P1

2.2 0.00741 0.0411 0.381457 0.999497 0.449587 0.999623 ULBP2 80328 A_23_P1

1.82 0.007477 0.041165 0.673118 0.999497 0.267142 0.999623 FBF1 85302 A_24_P7

1.81 0.007547 0.041205 0.530159 0.999497 0.324689 0.999623 TCIRG1 10312 A_23_P7

1.75 0.007515 0.041205 0.807324 0.999497 0.336722 0.999623 CUL2 8453 A_24_P2

−2.44 0.007571 0.041205 0.833332 0.999497 0.548846 0.999623 FOXO3 2309 A_32_P1

1.22 0.00758 0.041205 0.993458 0.999497 0.821457 0.999623 FKBP8 23770 A_23_P3

1.49 0.007665 0.041315 0.359148 0.999497 0.380361 0.999623 IFT172 26160 A_23_P4

1.53 0.00772 0.041315 0.703408 0.999497 0.597845 0.999623 RFX2 5990 A_23_P5

1.5 0.007694 0.041315 0.645075 0.999497 0.75437 0.999623 STX1A 6804 A_23_P8

1.46 0.007702 0.041315 0.364024 0.999497 0.258177 0.999623 BNIP1 662 A_23_P7

1.57 0.007629 0.041315 0.947384 0.999497 0.241845 0.999623 DAPK2 23604 A_24_P1

1.45 0.007805 0.041645 0.836353 0.999497 0.040823 0.999623 DYRK2 8445 A_23_P2

1.27 0.007862 0.04169 0.993595 0.999497 0.593907 0.999623 BBC3 27113 A_23_P3

1.49 0.007854 0.04169 0.652506 0.999497 0.695162 0.999623 FUT4 2526 A_24_P2

1.5 0.007921 0.041874 0.756507 0.999497 0.805845 0.999623 TH1L 51497 A_24_P2

1.38 0.008004 0.04218 0.570652 0.999497 0.640054 0.999623 CYTH2 9266 A_23_P1

1.51 0.008084 0.042473 0.265899 0.999497 0.921536 0.999623 MFAP4 4239 A_23_P1

1.62 0.008144 0.042661 0.820137 0.999497 0.810928 0.999623 IGFALS 3483 A_23_P1

1.76 0.008414 0.042748 0.869832 0.999497 0.649025 0.999623 CLDN4 1364 A_24_P1

2.13 0.008418 0.042748 0.578741 0.999497 0.743621 0.999623 RPS3A 6189 A_32_P1

−6.71 0.008272 0.042748 0.339463 0.999497 0.302119 0.999623 BIN3 55909 A_24_P1

1.69 0.008205 0.042748 0.221195 0.999497 0.308429 0.999623 BSG 682 A_24_P2

1.83 0.008386 0.042748 0.358983 0.999497 0.36206 0.999623 PCSK9 255738 A_32_P1

−2.31 0.008448 0.042748 0.87887 0.999497 0.858256 0.999623 YWHAG 7532 A_24_P1

−1.57 0.008284 0.042748 0.692892 0.999497 0.900717 0.999623 BCL2A1 597 A_23_P1

−2.14 0.008483 0.042748 0.894468 0.999497 0.539085 0.999623 CFB 629 A_23_P1

1.47 0.00835 0.042748 0.467483 0.999497 0.918707 0.999623 CROP 51747 A_24_P9

−2.88 0.008461 0.042748 0.799301 0.999497 0.839386 0.999623 MSLN 10232 A_23_P7

1.42 0.008228 0.042748 0.306015 0.999497 0.280281 0.999623 WWP2 11060 A_23_P2

1.46 0.008446 0.042748 0.560331 0.999497 0.465721 0.999623 CD200 4345 A_23_P1

1.63 0.008448 0.042748 0.25547 0.999497 0.901291 0.999623 PSMD12 5718 A_23_P7

−2.08 0.008603 0.043102 0.958158 0.999497 0.63048 0.999623 CCND3 896 A_23_P3

1.45 0.008629 0.043102 0.930372 0.999497 0.318564 0.999623 COL15A1 1306 A_24_P3

1.59 0.00862 0.043102 0.62631 0.999497 0.777929 0.999623 RAB3B 5865 A_32_P1

1.3 0.008685 0.043133 0.63651 0.999497 0.247465 0.999623 AIFM2 84883 A_32_P7

1.58 0.008675 0.043133 0.448982 0.999497 0.746676 0.999623 RPS6KA1 6195 A_24_P3

1.8 0.008792 0.043542 0.844551 0.999497 0.859124 0.999623 HIP1 3092 A_23_P7

1.42 0.00884 0.043652 0.984356 0.999497 0.706868 0.999623 ICAM2 3384 A_23_P1

1.38 0.008886 0.043754 0.574412 0.999497 0.773073 0.999623 ISLR2 57611 A_32_P3

−1.56 0.008919 0.043789 0.293109 0.999497 0.275047 0.999623 AGGF1 55109 A_24_P2

1.34 0.009025 0.043934 0.9808 0.999497 0.920873 0.999623 LIF 3976 A_24_P1

1.7 0.00901 0.043934 0.684537 0.999497 0.304884 0.999623 CDH7 1005 A_23_P1

1.3 0.009022 0.043934 0.744671 0.999497 0.93517 0.999623 GMDS 2762 A_23_P7

1.45 0.009147 0.04414 0.190757 0.999497 0.953153 0.999623 HSPA1A 3303 A_24_P1

1.75 0.009119 0.04414 0.770009 0.999497 0.281256 0.999623 ACSF3 197322 A_23_P2

1.47 0.009182 0.04414 0.7574 0.999497 0.979474 0.999623 SFRS17A 8227 A_24_P1

1.3 0.009348 0.04414 0.899318 0.999497 0.841563 0.999623 RBM4 5936 A_23_P1

1.64 0.009269 0.04414 0.686055 0.999497 0.901274 0.999623 XAF1 54739 A_23_P4

1.29 0.009205 0.04414 0.571241 0.999497 0.278729 0.999623 CD2BP2 10421 A_23_P6

2.43 0.009285 0.04414 0.864105 0.999497 0.924686 0.999623 TUBB 203068 A_23_P3

−1.27 0.009241 0.04414 0.701621 0.999497 0.433631 0.999623 WFIKKN1 117166 A_23_P1

1.79 0.009333 0.04414 0.882626 0.999497 0.983759 0.999623 MARK4 57787 A_23_P1

1.72 0.009295 0.04414 0.610972 0.999497 0.849994 0.999623 DOCK3 1795 A_24_P2

−2.09 0.009349 0.04414 0.99466 0.999497 0.096042 0.999623 TRAF7 84231 A_23_P2

1.68 0.009411 0.044311 0.612181 0.999497 0.292044 0.999623 HGF 3082 A_23_P9

1.52 0.009569 0.044882 0.198441 0.999497 0.50498 0.999623 EEF1A2 1917 A_23_P2

2.02 0.009584 0.044882 0.534017 0.999497 0.417562 0.999623 RAD9A 5883 A_23_P1

1.36 0.009796 0.044899 0.420983 0.999497 0.774342 0.999623 NDUFS1 4719 A_23_P1

−3.13 0.009784 0.044899 0.562165 0.999497 0.668457 0.999623 TAGAP 117289 A_23_P2

−3.04 0.009658 0.044899 0.280321 0.999497 0.521664 0.999623 TAX1BP1 8887 A_24_P9

−1.23 0.009719 0.044899 0.469163 0.999497 0.420653 0.999623 CD109 135228 A_23_P3

−2.13 0.009739 0.044899 0.814845 0.999497 0.336296 0.999623 TOLLIP 54472 A_23_P7

1.69 0.009629 0.044899 0.652502 0.999497 0.944066 0.999623 BCL11B 64919 A_23_P2

1.36 0.009749 0.044899 0.353575 0.999497 0.943937 0.999623 RTN3 10313 A_24_P3

1.38 0.009788 0.044899 0.58224 0.999497 0.571566 0.999623 PVRL3 25945 A_23_P8

−1.62 0.009854 0.045045 0.330796 0.999497 0.450665 0.999623 ERBB3 2065 A_24_P9

1.37 0.009892 0.045098 0.444707 0.999497 0.606208 0.999623 TTYH1 57348 A_23_P5

1.81 0.01008 0.04524 0.513414 0.999497 0.981078 0.999623 TCF3 6929 A_24_P3

1.64 0.009991 0.04524 0.628151 0.999497 0.54057 0.999623 PCMT1 5110 A_24_P1

−1.81 0.010046 0.04524 0.841975 0.999497 0.613309 0.999623 NLGN3 54413 A_23_P6

1.44 0.010021 0.04524 0.535075 0.999497 0.603253 0.999623 NRXN2 9379 A_24_P2

1.44 0.01008 0.04524 0.623422 0.999497 0.420966 0.999623 GTF2H2 2966 A_24_P2

−1.57 0.009963 0.04524 0.661375 0.999497 0.218962 0.999623 GNA12 2768 A_23_P2

1.45 0.010123 0.045312 0.603611 0.999497 0.392406 0.999623 TNFRSF1A 7132 A_24_P3

1.71 0.010194 0.045513 0.669489 0.999497 0.685361 0.999623 PTGIS 5740 A_24_P4

−2.43 0.010325 0.045576 0.652291 0.999497 0.282921 0.999623 AXIN1 8312 A_24_P2

1.58 0.010341 0.045576 0.652531 0.999497 0.43497 0.999623 C9orf61 9413 A_24_P2

1.31 0.010306 0.045576 0.14166 0.999497 0.930086 0.999623 CCL17 6361 A_23_P2

1.39 0.010272 0.045576 0.764709 0.999497 0.247562 0.999623 TSTA3 7264 A_23_P9

1.47 0.010236 0.045576 0.571615 0.999497 0.867314 0.999623 BOK 666 A_23_P2

1.79 0.010547 0.045815 0.590899 0.999497 0.212588 0.999623 MLLT1 4298 A_24_P4

1.52 0.010509 0.045815 0.785998 0.999497 0.587068 0.999623 CMKLR1 1240 A_24_P7

1.55 0.010444 0.045815 0.723016 0.999497 0.43937 0.999623 MST1R 4486 A_23_P2

1.81 0.010581 0.045815 0.49545 0.999497 0.541623 0.999623 FGFR3 2261 A_23_P5

1.33 0.010471 0.045815 0.591985 0.999497 0.728747 0.999623 C1QTNF6 114904 A_24_P2

1.86 0.010542 0.045815 0.797733 0.999497 0.521666 0.999623 ITFG2 55846 A_24_P1

1.52 0.010559 0.045815 0.872446 0.999497 0.184621 0.999623 KCNH3 23416 A_23_P8

1.49 0.010616 0.045853 0.716099 0.999497 0.361986 0.999623 AGPAT2 10555 A_32_P2

2.16 0.011394 0.046008 0.883506 0.999497 0.932464 0.999623 MACF1 23499 A_24_P4

1.24 0.011639 0.046008 0.413313 0.999497 0.755876 0.999623 MAMDC4 158056 A_23_P7

1.69 0.01093 0.046008 0.885796 0.999497 0.33709 0.999623 ITGB2 3689 A_23_P3

−2.6 0.011337 0.046008 0.577022 0.999497 0.1366 0.999623 DGKZ 8525 A_24_P1

1.75 0.011766 0.046008 0.683759 0.999497 0.658028 0.999623 SLC26A6 65010 A_23_P1

1.44 0.010777 0.046008 0.990628 0.999497 0.929937 0.999623 AP2A2 161 A_24_P3

1.3 0.011777 0.046008 0.758622 0.999497 0.071888 0.999623 LAIR1 3903 A_23_P2

1.3 0.011816 0.046008 0.798188 0.999497 0.445371 0.999623 SIX4 51804 A_23_P3

1.31 0.011577 0.046008 0.662808 0.999497 0.967053 0.999623 7-Sep 989 A_32_P7

−2.54 0.011163 0.046008 0.707334 0.999497 0.548829 0.999623 IL23A 51561 A_23_P7

2.19 0.011657 0.046008 0.795485 0.999497 0.601849 0.999623 CLDN12 9069 A_23_P1

−1.75 0.011527 0.046008 0.952433 0.999497 0.187921 0.999623 NFE2L3 9603 A_23_P4

−2.04 0.011594 0.046008 0.30672 0.999497 0.699681 0.999623 AR 367 A_23_P1

1.41 0.011739 0.046008 0.722581 0.999497 0.845551 0.999623 FGFR1 2260 A_23_P3

−4.3 0.011933 0.046008 0.416966 0.999497 0.640217 0.999623 FASTKD2 22868 A_23_P3

−2.68 0.011045 0.046008 0.644005 0.999497 0.302389 0.999623 MYH9 4627 A_23_P5

1.76 0.011765 0.046008 0.422758 0.999497 0.886066 0.999623 SLPI 6590 A_23_P9

1.43 0.011265 0.046008 0.209007 0.999497 0.089489 0.999623 LATS2 26524 A_24_P7

1.39 0.011702 0.046008 0.492726 0.999497 0.538383 0.999623 RPS6KA2 6196 A_23_P3

1.52 0.011932 0.046008 0.780008 0.999497 0.445324 0.999623 CD19 930 A_23_P1

2.19 0.010793 0.046008 0.213669 0.999497 0.834861 0.999623 CD3EAP 10849 A_23_P2

1.73 0.011621 0.046008 0.718564 0.999497 0.703033 0.999623 ADAR 103 A_23_P2

1.71 0.011759 0.046008 0.872095 0.999497 0.997358 0.999623 PRKACA 5566 A_24_P3

1.82 0.011515 0.046008 0.936106 0.999497 0.030038 0.999623 C1QTNF2 114898 A_23_P9

1.56 0.011866 0.046008 0.975072 0.999497 0.524615 0.999623 FIS1 51024 A_23_P2

2.08 0.010736 0.046008 0.956333 0.999497 0.517864 0.999623 MST1 4485 A_24_P1

1.48 0.011737 0.046008 0.520318 0.999497 0.219025 0.999623 MYD88 4615 A_23_P9

1.66 0.011705 0.046008 0.627416 0.999497 0.473691 0.999623 CLDN3 1365 A_23_P7

1.73 0.011827 0.046008 0.959934 0.999497 0.150042 0.999623 FCGRT 2217 A_23_P5

1.49 0.010887 0.046008 0.871968 0.999497 0.733417 0.999623 PLAUR 5329 A_23_P1

1.72 0.011721 0.046008 0.913173 0.999497 0.959682 0.999623 NFAT5 10725 A_23_P3

−1.59 0.01097 0.046008 0.927355 0.999497 0.231058 0.999623 RNF130 55819 A_23_P4

−1.54 0.011328 0.046008 0.624961 0.999497 0.199011 0.999623 JMY 133746 A_32_P1

−1.6 0.010749 0.046008 0.993441 0.999497 0.897651 0.999623 PHLDA1 22822 A_24_P9

−1.65 0.011663 0.046008 0.623252 0.999497 0.22338 0.999623 UBE2Z 65264 A_24_P3

−1.4 0.011561 0.046008 0.35366 0.999497 0.76336 0.999623 EHD1 10938 A_23_P5

1.19 0.011932 0.046008 0.556726 0.999497 0.933536 0.999623 RFX5 5993 A_24_P2

−1.43 0.011832 0.046008 0.714182 0.999497 0.443883 0.999623 LTBR 4055 A_23_P5

1.35 0.010873 0.046008 0.74031 0.999497 0.870839 0.999623 SNX17 9784 A_23_P2

1.37 0.011097 0.046008 0.678232 0.999497 0.817956 0.999623 GDF15 9518 A_23_P1

1.62 0.011923 0.046008 0.701642 0.999497 0.446223 0.999623 NME3 4832 A_23_P1

1.57 0.011402 0.046008 0.626596 0.999497 0.245007 0.999623 TBX21 30009 A_23_P1

−1.38 0.011205 0.046008 0.593257 0.999497 0.823812 0.999623 SOCS3 9021 A_23_P3

1.28 0.011613 0.046008 0.839539 0.999497 0.088534 0.999623 WISP1 8840 A_23_P3

1.49 0.010885 0.046008 0.685025 0.999497 0.867964 0.999623 CDC2L2 728642 A_24_P9

1.32 0.010948 0.046008 0.942452 0.999497 0.499853 0.999623 YWHAZ 7534 A_32_P9

−1.79 0.010923 0.046008 0.39737 0.999497 0.535257 0.999623 MAPK7 5598 A_23_P1

1.5 0.01148 0.046008 0.334768 0.999497 0.64556 0.999623 CDC2L1 984 A_23_P5

1.72 0.011987 0.046113 0.709495 0.999497 0.893553 0.999623 PIWIL4 143689 A_23_P4

1.51 0.012061 0.046291 0.854777 0.999497 0.737882 0.999623 ADRB3 155 A_23_P1

−1.31 0.012105 0.046359 0.665715 0.999497 0.527794 0.999623 DDIT4 54541 A_32_P2

1.48 0.01217 0.0464 0.785068 0.999497 0.665712 0.999623 CALR 811 A_24_P6

1.28 0.012168 0.0464 0.048403 0.999497 0.792997 0.999623 SOCS7 30837 A_32_P4

1.72 0.012371 0.046958 0.968504 0.999497 0.879769 0.999623 METTL11A 28989 A_23_P7

1.48 0.012369 0.046958 0.474362 0.999497 0.648279 0.999623 TNFAIP3 7128 A_24_P1

−1.59 0.012484 0.047179 0.670444 0.999497 0.430055 0.999623 EP300 2033 A_23_P4

−2.34 0.012471 0.047179 0.102764 0.999497 0.444003 0.999623 LYST 1130 A_23_P3

−2.23 0.012682 0.047422 0.643012 0.999497 0.597959 0.999623 PACSIN1 29993 A_24_P1

1.44 0.012592 0.047422 0.810806 0.999497 0.319026 0.999623 IGHMBP2 3508 A_23_P3

1.86 0.012685 0.047422 0.536694 0.999497 0.559356 0.999623 POLM 27434 A_24_P9

1.73 0.012615 0.047422 0.74306 0.999497 0.630574 0.999623 LRP4 4038 A_24_P4

−1.89 0.01267 0.047422 0.385702 0.999497 0.259541 0.999623 NLK 51701 A_23_P1

1.57 0.012716 0.047431 0.959462 0.999497 0.362725 0.999623 RAG1AP1 55974 A_24_P8

1.63 0.012996 0.047513 0.825239 0.999497 0.72817 0.999623 RAF1 5894 A_23_P4

1.4 0.013268 0.047513 0.604929 0.999497 0.864017 0.999623 LEFTY2 7044 A_23_P1

1.35 0.013316 0.047513 0.835132 0.999497 0.79175 0.999623 KLRF1 51348 A_32_P1

−2.47 0.013194 0.047513 0.094166 0.999497 0.497135 0.999623 BAT3 7917 A_23_P1

1.44 0.013123 0.047513 0.830021 0.999497 0.605435 0.999623 GADD45B 4616 A_23_P1

1.67 0.013118 0.047513 0.418033 0.999497 0.561697 0.999623 ITGB4 3691 A_23_P6

1.88 0.012977 0.047513 0.884416 0.999497 0.850481 0.999623 NDRG1 10397 A_24_P3

1.39 0.013316 0.047513 0.431376 0.999497 0.338149 0.999623 FOXL2 668 A_23_P1

1.4 0.01325 0.047513 0.623953 0.999497 0.756941 0.999623 CRKL 1399 A_24_P9

−3.21 0.013096 0.047513 0.989163 0.999497 0.618805 0.999623 FKBP5 2289 A_23_P1

1.48 0.013028 0.047513 0.805064 0.999497 0.180509 0.999623 L1CAM 3897 A_24_P2

1.48 0.012946 0.047513 0.948151 0.999497 0.973372 0.999623 BAG3 9531 A_23_P5

−1.99 0.013304 0.047513 0.889016 0.999497 0.9404 0.999623 RHOA 387 A_23_P6

1.53 0.01318 0.047513 0.672895 0.999497 0.646367 0.999623 SMAD6 4091 A_23_P6

1.71 0.012827 0.047513 0.844195 0.999497 0.658975 0.999623 GPR98 84059 A_24_P1

−1.41 0.012977 0.047513 0.684207 0.999497 0.179322 0.999623 IRS2 8660 A_23_P5

1.5 0.012997 0.047513 0.942002 0.999497 0.602622 0.999623 PML 5371 A_24_P1

1.3 0.013099 0.047513 0.879069 0.999497 0.92679 0.999623 PACS2 23241 A_24_P3

1.75 0.013226 0.047513 0.433797 0.999497 0.355999 0.999623 PSMD9 5715 A_23_P2

1.31 0.013234 0.047513 0.457114 0.999497 0.757866 0.999623 SOCS1 8651 A_23_P4

1.25 0.012857 0.047513 0.596738 0.999497 0.43267 0.999623 EP300 2033 A_24_P7

1.29 0.013457 0.047522 0.518843 0.999497 0.836977 0.999623 MLL5 55904 A_24_P1

−2.12 0.013431 0.047522 0.853142 0.999497 0.367771 0.999623 SH2D1A 4068 A_24_P2

−1.53 0.013432 0.047522 0.354116 0.999497 0.768015 0.999623 UBP1 7342 A_23_P2

−1.91 0.013397 0.047522 0.864577 0.999497 0.584273 0.999623 CLN8 2055 A_23_P2

1.35 0.013435 0.047522 0.97432 0.999497 0.823165 0.999623 NOL3 8996 A_23_P2

1.28 0.01352 0.047649 0.885717 0.999497 0.216732 0.999623 MKL1 57591 A_23_P3

1.28 0.013636 0.047959 0.213954 0.999497 0.218478 0.999623 PSMB2 5690 A_23_P1

1.66 0.013703 0.048095 0.172869 0.999497 0.889876 0.999623 IBTK 25998 A_23_P3

−1.49 0.013747 0.048101 0.847817 0.999497 0.427783 0.999623 CAT 847 A_23_P1

1.32 0.01376 0.048101 0.349021 0.999497 0.498228 0.999623 NTN1 9423 A_32_P5

1.57 0.013797 0.04813 0.625534 0.999497 0.525615 0.999623 TNF 7124 A_24_P5

1.42 0.013975 0.048193 0.496325 0.999497 0.252806 0.999623 DBNL 28988 A_24_P4

1.87 0.013971 0.048193 0.962298 0.999497 0.497226 0.999623 RABEP1 9135 A_23_P7

−2.29 0.014175 0.048193 0.230644 0.999497 0.897774 0.999623 HFE 3077 A_23_P1

−2.54 0.014178 0.048193 0.90836 0.999497 0.616177 0.999623 POLD1 5424 A_23_P5

1.54 0.01398 0.048193 0.577717 0.999497 0.748243 0.999623 DDR1 780 A_23_P9

1.81 0.014078 0.048193 0.549439 0.999497 0.982262 0.999623 ZFYVE9 9372 A_23_P3

1.31 0.014041 0.048193 0.24404 0.999497 0.234146 0.999623 SNAP29 9342 A_23_P2

−2.08 0.013989 0.048193 0.833414 0.999497 0.455003 0.999623 AQP3 360 A_23_P1

1.54 0.014039 0.048193 0.469185 0.999497 0.622415 0.999623 PSMF1 9491 A_24_P1

1.26 0.014135 0.048193 0.850782 0.999497 0.82084 0.999623 PBX4 80714 A_23_P9

1.33 0.013989 0.048193 0.228749 0.999497 0.538604 0.999623 BDNF 627 A_23_P1

1.41 0.014073 0.048193 0.323296 0.999497 0.764656 0.999623 COL7A1 1294 A_23_P1

1.66 0.014106 0.048193 0.54834 0.999497 0.460984 0.999623 ATP2A2 488 A_24_P1

1.32 0.014283 0.048454 0.164309 0.999497 0.215689 0.999623 SRPK1 6732 A_23_P1

−1.64 0.014417 0.048811 0.938567 0.999497 0.575052 0.999623 NISCH 11188 A_24_P9

1.46 0.014487 0.048916 0.914042 0.999497 0.524538 0.999623 AMOTL1 154810 A_23_P1

1.7 0.014504 0.048916 0.441658 0.999497 0.566352 0.999623 PKN2 5586 A_24_P3

−1.51 0.014633 0.049157 0.651112 0.999497 0.540453 0.999623 ICAM5 7087 A_24_P2

1.64 0.014627 0.049157 0.709284 0.999497 0.406186 0.999623 LTBP2 4053 A_23_P4

1.55 0.014726 0.049278 0.78761 0.999497 0.050492 0.999623 PDCD10 11235 A_23_P1

−2.23 0.014706 0.049278 0.219256 0.999497 0.625871 0.999623 EMR1 2015 A_23_P2

1.39 0.014778 0.049356 0.461514 0.999497 0.088336 0.999623 HSPB1 3315 A_24_P8

1.64 0.014813 0.049377 0.895272 0.999497 0.507419 0.999623 RAB4A 5867 A_24_P1

−1.9 0.014942 0.049477 0.68528 0.999497 0.805571 0.999623 PSMG3 84262 A_24_P2

1.33 0.014935 0.049477 0.509811 0.999497 0.910752 0.999623 CD86 942 A_23_P1

−2.1 0.015025 0.049477 0.47095 0.999497 0.349895 0.999623 COTL1 23406 A_23_P8

1.63 0.015133 0.049477 0.104524 0.999497 0.467965 0.999623 TUBB 203068 A_23_P8

1.34 0.015187 0.049477 0.24464 0.999497 0.530503 0.999623 COL6A1 1291 A_32_P3

1.43 0.015105 0.049477 0.427278 0.999497 0.481937 0.999623 CEACAM19 56971 A_23_P7

1.84 0.01516 0.049477 0.546633 0.999497 0.168758 0.999623 UBE2Z 65264 A_24_P3

1.77 0.015088 0.049477 0.981491 0.999497 0.894359 0.999623 ENG 2022 A_23_P8

1.56 0.01488 0.049477 0.853209 0.999497 0.622503 0.999623 NAIF1 203245 A_24_P8

1.59 0.014961 0.049477 0.447055 0.999497 0.609572 0.999623 FAM3C 10447 A_23_P1

−1.83 0.015015 0.049477 0.979811 0.999497 0.749666 0.999623 SCFD2 152579 A_23_P9

1.67 0.015134 0.049477 0.884615 0.999497 0.762606 0.999623 FOXC1 2296 A_23_P3

1.56 0.015239 0.049551 0.742861 0.999497 0.263313 0.999623 RPS3 6188 A_23_P1

1.39 0.01535 0.049784 0.6263 0.999497 0.27172 0.999623 PNN 5411 A_32_P2

1.9 0.015455 0.049784 0.701619 0.999497 0.099695 0.999623 LPP 4026 A_24_P1

−1.89 0.0154 0.049784 0.3246 0.999497 0.596791 0.999623 YWHAZ 7534 A_32_P1

−1.55 0.015381 0.049784 0.564362 0.999497 0.865171 0.999623 TAPBPL 55080 A_23_P3

1.47 0.015437 0.049784 0.46879 0.999497 0.870077 0.999623 PYDC1 260434 A_23_P4

1.55 0.015517 0.049856 0.859028 0.999497 0.294833 0.999623 MAP2K3 5606 A_24_P2

1.96 0.015535 0.049856 0.576898 0.999497 0.357913 0.999623 DOCK11 139818 A_23_P1

−1.9 0.015696 0.049953 0.636569 0.999497 0.855811 0.999623 HTATIP2 10553 A_23_P6

−1.58 0.015739 0.049953 0.869306 0.999497 0.459502 0.999623 SRF 6722 A_24_P3

−2.44 0.015601 0.049953 0.792965 0.999497 0.702688 0.999623 HDAC4 9759 A_24_P8

−2.51 0.015763 0.049953 0.362259 0.999497 0.877712 0.999623 SP3 6670 A_23_P3

−1.77 0.015825 0.049953 0.80038 0.999497 0.197154 0.999623 MAP1S 55201 A_23_P6

1.81 0.01571 0.049953 0.549605 0.999497 0.360408 0.999623 FEN1 2237 A_24_P7

1.5 0.015928 0.049953 0.634676 0.999497 0.246327 0.999623 NISCH 11188 A_24_P4

1.68 0.015908 0.049953 0.53073 0.999497 0.589713 0.999623 HAX1 10456 A_23_P1

1.51 0.015846 0.049953 0.520141 0.999497 0.27338 0.999623 RASSF5 83593 A_24_P1

−1.42 0.015661 0.049953 0.617751 0.999497 0.722341 0.999623 GNLY 10578 A_23_P2

−3.67 0.015862 0.049953 0.540932 0.999497 0.6485 0.999623 STK17A 9263 A_23_P8

1.19 0.015943 0.049953 0.186936 0.999497 0.471213 0.999623 THAP3 90326 A_23_P3

1.84 0.015971 0.049953 0.340718 0.999497 0.544535 0.999623 TREML2 79865 A_23_P7

2.03 0.015817 0.049953 0.440179 0.999497 0.775578 0.999623 HMGB1 3146 A_24_P8

−1.38 0.016067 0.050069 0.52182 0.999497 0.148462 0.999623 MYO18A 399687 A_23_P7

1.29 0.016065 0.050069 0.998903 0.999497 0.324238 0.999623 DUB3 377630 A_24_P2

−1.85 0.016161 0.050192 0.196264 0.999497 0.491006 0.999623 XRCC5 7520 A_24_P3

−1.63 0.016194 0.050192 0.659552 0.999497 0.398873 0.999623 PDCD6IP 10015 A_24_P9

−2.76 0.01618 0.050192 0.720101 0.999497 0.279458 0.999623 PANX1 24145 A_23_P4

1.41 0.016242 0.050251 0.417255 0.999497 0.488458 0.999623 CD40 958 A_23_P5

1.54 0.016274 0.050262 0.589716 0.999497 0.824097 0.999623 PAFAH1B1 5048 A_24_P3

−1.47 0.016423 0.050509 0.567136 0.999497 0.712043 0.999623 EFS 10278 A_23_P4

1.45 0.016397 0.050509 0.59346 0.999497 0.817169 0.999623 LMNA 4000 A_24_P1

1.41 0.016472 0.050509 0.591051 0.999497 0.698601 0.999623 GDF3 9573 A_23_P7

1.76 0.016448 0.050509 0.454274 0.999497 0.873001 0.999623 MLL4 9757 A_23_P1

1.81 0.01651 0.050536 0.663526 0.999497 0.484866 0.999623 RABEP2 79874 A_23_P6

1.62 0.016647 0.050686 0.72717 0.999497 0.505663 0.999623 IRAK1BP1 134728 A_32_P2

−1.63 0.016622 0.050686 0.873052 0.999497 0.271013 0.999623 EPS15L1 58513 A_23_P3

1.37 0.016609 0.050686 0.558181 0.999497 0.997655 0.999623 SERPINF2 5345 A_23_P8

1.78 0.016727 0.050841 0.751593 0.999497 0.417585 0.999623 RACGAP1 29127 A_32_P1

−2.21 0.016765 0.050865 0.333038 0.999497 0.999402 0.999623 AP3B2 8120 A_23_P7

1.52 0.01684 0.051003 0.851386 0.999497 0.57374 0.999623 GYG2 8908 A_32_P1

1.45 0.016875 0.05102 0.530844 0.999497 0.142388 0.999623 CBL 867 A_23_P3

1.56 0.016983 0.051041 0.806197 0.999497 0.899872 0.999623 SYNJ2BP 55333 A_24_P2

1.51 0.016967 0.051041 0.798666 0.999497 0.981506 0.999623 DLC1 10395 A_24_P9

−1.95 0.017 0.051041 0.843286 0.999497 0.450104 0.999623 CREBBP 1387 A_24_P3

−2.25 0.016942 0.051041 0.817713 0.999497 0.419253 0.999623 DST 667 A_23_P5

1.41 0.017075 0.051142 0.296653 0.999497 0.711256 0.999623 CELSR3 1951 A_23_P9

1.4 0.017093 0.051142 0.982517 0.999497 0.820933 0.999623 LRDD 55367 A_32_P1

1.67 0.017205 0.051298 0.928012 0.999497 0.404034 0.999623 HIVEP3 59269 A_24_P8

1.4 0.017179 0.051298 0.892249 0.999497 0.356162 0.999623 ITIH1 3697 A_23_P1

1.37 0.01738 0.051376 0.611713 0.999497 0.22151 0.999623 SPG7 6687 A_24_P5

1.49 0.01738 0.051376 0.689204 0.999497 0.774355 0.999623 BMP4 652 A_23_P5

1.46 0.017375 0.051376 0.348872 0.999497 0.686438 0.999623 HLA-DMA 3108 A_23_P4

1.72 0.017325 0.051376 0.270348 0.999497 0.921517 0.999623 CUL4A 8451 A_24_P6

−1.51 0.017319 0.051376 0.427646 0.999497 0.363818 0.999623 S100B 6285 A_23_P1

−2.33 0.017479 0.051579 0.383508 0.999497 0.47419 0.999623 HIPK2 28996 A_24_P6

−2.02 0.017655 0.051664 0.880894 0.999497 0.189806 0.999623 TRIP6 7205 A_24_P4

1.32 0.017616 0.051664 0.224741 0.999497 0.413981 0.999623 RPSA 3921 A_24_P3

−2.29 0.017658 0.051664 0.689339 0.999497 0.494854 0.999623 TNFRSF8 943 A_23_P5

1.47 0.01763 0.051664 0.713048 0.999497 0.355213 0.999623 DHCR24 1718 A_23_P3

−1.44 0.017589 0.051664 0.997665 0.999497 0.603534 0.999623 GCNT2 2651 A_24_P3

−2.02 0.017693 0.051681 0.851155 0.999497 0.51601 0.999623 ACSF3 197322 A_32_P2

1.4 0.017812 0.05185 0.800768 0.999497 0.64634 0.999623 LRIG1 26018 A_23_P1

1.46 0.01779 0.05185 0.625735 0.999497 0.191008 0.999623 UBL7 84993 A_23_P1

1.61 0.017843 0.051854 0.592493 0.999497 0.553974 0.999623 NEDD4L 23327 A_24_P1

−1.48 0.017927 0.051924 0.54472 0.999497 0.482055 0.999623 TRAF2 7186 A_23_P1

1.64 0.017906 0.051924 0.661343 0.999497 0.861379 0.999623 CXCL12 6387 A_23_P2

1.34 0.018001 0.05205 0.543554 0.999497 0.423963 0.999623 DPT 1805 A_23_P2

−1.63 0.018103 0.05217 0.605565 0.999497 0.072208 0.999623 MFGE8 4240 A_23_P4

1.43 0.018092 0.05217 0.64808 0.999497 0.524613 0.999623 C1RL 51279 A_23_P3

−1.83 0.01829 0.052194 0.975317 0.999497 0.171012 0.999623 JAK1 3716 A_23_P9

1.29 0.018292 0.052194 0.796622 0.999497 0.631485 0.999623 HDAC3 8841 A_23_P7

1.46 0.018293 0.052194 0.745046 0.999497 0.560529 0.999623 NF2 4771 A_23_P2

−1.31 0.018246 0.052194 0.953115 0.999497 0.791877 0.999623 PPIH 10465 A_23_P2

1.37 0.018156 0.052194 0.800519 0.999497 0.687063 0.999623 DAP 1611 A_24_P2

1.68 0.018176 0.052194 0.254917 0.999497 0.998228 0.999623 RASSF5 83593 A_24_P3

1.42 0.018386 0.052374 0.217375 0.999497 0.6456 0.999623 FGB 2244 A_23_P1

−1.76 0.018452 0.052473 0.941636 0.999497 0.641752 0.999623 COL9A1 1297 A_24_P3

1.73 0.018791 0.052571 0.535609 0.999497 0.292217 0.999623 MIA3 375056 A_24_P2

−1.52 0.018669 0.052571 0.963688 0.999497 0.563596 0.999623 AGGF1 55109 A_23_P2

−1.57 0.018757 0.052571 0.525892 0.999497 0.321101 0.999623 ANLN 54443 A_23_P3

−1.83 0.018522 0.052571 0.911901 0.999497 0.453283 0.999623 PKN3 29941 A_23_P2

1.55 0.018662 0.052571 0.967297 0.999497 0.534119 0.999623 CES1 1066 A_23_P2

1.28 0.018566 0.052571 0.989327 0.999497 0.31366 0.999623 PSMD2 5708 A_24_P4

1.3 0.018693 0.052571 0.734936 0.999497 0.85722 0.999623 CDK5 1020 A_23_P8

1.36 0.018722 0.052571 0.948372 0.999497 0.902436 0.999623 RAB7A 7879 A_24_P2

1.38 0.018778 0.052571 0.685641 0.999497 0.748355 0.999623 SH3GL2 6456 A_23_P1

1.26 0.018774 0.052571 0.99059 0.999497 0.3713 0.999623 LENG9 94059 A_32_P4

−1.43 0.018823 0.052573 0.995231 0.999497 0.049609 0.999623 MNDA 4332 A_23_P1

−3.26 0.019013 0.052678 0.201131 0.999497 0.820534 0.999623 GZMB 3002 A_23_P1

−4.13 0.01891 0.052678 0.95404 0.999497 0.727099 0.999623 TMBIM6 7009 A_23_P2

1.65 0.018934 0.052678 0.912088 0.999497 0.730606 0.999623 EXOC4 60412 A_24_P7

−1.32 0.018975 0.052678 0.297355 0.999497 0.26402 0.999623 BAG4 9530 A_24_P9

−2.5 0.018999 0.052678 0.909919 0.999497 0.568578 0.999623 LTBP4 8425 A_23_P1

1.75 0.019121 0.052893 0.663471 0.999497 0.710995 0.999623 DHCR24 1718 A_23_P2

1.81 0.019155 0.052901 0.890871 0.999497 0.400115 0.999623 COL8A1 1295 A_23_P6

1.36 0.019206 0.052957 0.791072 0.999497 0.614035 0.999623 INHBB 3625 A_23_P1

1.23 0.019281 0.053079 0.403749 0.999497 0.971628 0.999623 RPS3A 6189 A_24_P3

−1.67 0.019398 0.053231 0.794357 0.999497 0.502794 0.999623 CLCF1 23529 A_23_P1

1.52 0.019385 0.053231 0.826001 0.999497 0.909078 0.999623 DGKE 8526 A_32_P5

1.56 0.019464 0.053328 0.972552 0.999497 0.771683 0.999623 AKT1 207 A_23_P2

1.7 0.019564 0.053495 0.786708 0.999497 0.686243 0.999623 SMAD4 4089 A_23_P2

−1.7 0.019649 0.053495 0.502666 0.999497 0.175732 0.999623 GPR77 27202 A_23_P1

1.57 0.019626 0.053495 0.491916 0.999497 0.410461 0.999623 RABEP1 9135 A_24_P9

−1.66 0.01964 0.053495 0.612789 0.999497 0.396126 0.999623 CDC42 998 A_23_P2

−1.77 0.019749 0.053533 0.22318 0.999497 0.780298 0.999623 RTN3 10313 A_32_P6

1.39 0.019788 0.053533 0.690649 0.999497 0.264794 0.999623 LOC728613 728613 A_24_P5

1.34 0.019784 0.053533 0.217679 0.999497 0.20341 0.999623 SHB 6461 A_23_P2

1.48 0.019711 0.053533 0.841275 0.999497 0.778223 0.999623 ELMO2 63916 A_24_P1

1.56 0.019866 0.053541 0.768714 0.999497 0.638768 0.999623 DGCR6 8214 A_24_P2

1.55 0.019884 0.053541 0.942565 0.999497 0.58851 0.999623 CCR6 1235 A_24_P2

−2.17 0.019826 0.053541 0.156564 0.999497 0.297857 0.999623 LAMA5 3911 A_32_P1

1.79 0.01993 0.053582 0.84655 0.999497 0.81709 0.999623 PRKAR1B 5575 A_32_P7

1.71 0.020007 0.053624 0.626371 0.999497 0.149768 0.999623 AMIGO1 57463 A_24_P3

1.27 0.020008 0.053624 0.7741 0.999497 0.90952 0.999623 KRAS 3845 A_23_P4

−1.85 0.020192 0.054035 0.391977 0.999497 0.399416 0.999623 KNG1 3827 A_23_P2

1.29 0.020374 0.054369 0.984157 0.999497 0.945638 0.999623 LDLRAP1 26119 A_32_P2

1.59 0.020381 0.054369 0.413619 0.999497 0.848391 0.999623 PSME3 10197 A_24_P3

1.47 0.020416 0.054381 0.134221 0.999497 0.588152 0.999623 RAB35 11021 A_23_P2

1.41 0.020663 0.054867 0.925716 0.999497 0.900051 0.999623 CCL27 10850 A_23_P1

1.32 0.020634 0.054867 0.555063 0.999497 0.607125 0.999623 FNBP1 23048 A_24_P2

−1.59 0.020837 0.054915 0.943748 0.999497 0.374231 0.999623 HIF1A 3091 A_24_P5

−2.63 0.020904 0.054915 0.506111 0.999497 0.425761 0.999623 MIF 4282 A_23_P9

2.35 0.020884 0.054915 0.9379 0.999497 0.170699 0.999623 IFRD1 3475 A_24_P1

−2.06 0.020772 0.054915 0.481302 0.999497 0.634188 0.999623 MARK3 4140 A_23_P1

1.19 0.020904 0.054915 0.495457 0.999497 0.35198 0.999623 CASP8AP2 9994 A_23_P5

−1.67 0.020872 0.054915 0.960732 0.999497 0.48113 0.999623 BCL6B 255877 A_23_P3

1.32 0.02081 0.054915 0.396926 0.999497 0.719695 0.999623 BCL9L 283149 A_24_P1

1.51 0.021124 0.055409 0.748984 0.999497 0.274008 0.999623 BTBD9 114781 A_32_P9

1.64 0.021164 0.055417 0.738167 0.999497 0.28085 0.999623 RAB26 25837 A_23_P5

1.63 0.021191 0.055417 0.93245 0.999497 0.670129 0.999623 HIP1 3092 A_24_P9

−1.85 0.02134 0.055721 0.575538 0.999497 0.250488 0.999623 TERF1 7013 A_24_P1

−2.32 0.021372 0.055721 0.515626 0.999497 0.892773 0.999623 GATA2 2624 A_24_P1

1.63 0.021461 0.055826 0.764621 0.999497 0.351429 0.999623 COL6A2 1292 A_23_P3

1.99 0.021477 0.055826 0.796434 0.999497 0.64886 0.999623 MAP4K4 9448 A_23_P1

−1.87 0.021568 0.055977 0.877988 0.999497 0.58069 0.999623 PXN 5829 A_32_P4

2 0.021875 0.056142 0.938061 0.999497 0.319663 0.999623 IGKC 3514 A_32_P1

1.69 0.022022 0.056142 0.701558 0.999497 0.329592 0.999623 TLX2 3196 A_23_P3

1.7 0.021845 0.056142 0.775794 0.999497 0.77374 0.999623 NTSR1 4923 A_23_P3

1.39 0.021794 0.056142 0.614617 0.999497 0.235568 0.999623 NFATC3 4775 A_23_P7

1.87 0.021799 0.056142 0.819628 0.999497 0.865093 0.999623 JAK3 3718 A_24_P5

1.59 0.021816 0.056142 0.490451 0.999497 0.687042 0.999623 PTPRS 5802 A_23_P5

1.33 0.021992 0.056142 0.073697 0.999497 0.028188 0.999623 SEMA4C 54910 A_23_P9

1.45 0.02197 0.056142 0.748578 0.999497 0.521656 0.999623 IFT81 28981 A_23_P7

−1.72 0.021961 0.056142 0.815794 0.999497 0.46504 0.999623 WWTR1 25937 A_23_P2

1.19 0.021808 0.056142 0.267907 0.999497 0.815463 0.999623 MSN 4478 A_24_P1

1.55 0.021903 0.056142 0.463843 0.999497 0.300839 0.999623 IL4I1 259307 A_23_P5

1.43 0.021876 0.056142 0.798508 0.999497 0.4201 0.999623 NFKBIB 4793 A_24_P1

1.65 0.022342 0.056377 0.878305 0.999497 0.860706 0.999623 MAG 4099 A_24_P2

1.39 0.022377 0.056377 0.568829 0.999497 0.090688 0.999623 ARHGAP27 201176 A_23_P1

1.5 0.022406 0.056377 0.316917 0.999497 0.27609 0.999623 PTPRU 10076 A_23_P1

1.51 0.022407 0.056377 0.669712 0.999497 0.772528 0.999623 HSPB1 3315 A_23_P2

1.66 0.022296 0.056377 0.800525 0.999497 0.236396 0.999623 MAL 4118 A_23_P1

1.38 0.022409 0.056377 0.240071 0.999497 0.979282 0.999623 SPIN2B 474343 A_23_P1

1.29 0.022305 0.056377 0.56812 0.999497 0.280096 0.999623 MED1 5469 A_23_P4

1.93 0.022333 0.056377 0.70843 0.999497 0.564714 0.999623 RHOT2 89941 A_23_P1

1.5 0.022339 0.056377 0.901844 0.999497 0.343098 0.999623 PAG1 55824 A_32_P6

−1.44 0.022711 0.056646 0.96324 0.999497 0.93506 0.999623 STEAP2 261729 A_23_P4

−1.5 0.022586 0.056646 0.482959 0.999497 0.664367 0.999623 NPTN 27020 A_24_P9

1.48 0.022781 0.056646 0.703564 0.999497 0.976427 0.999623 ORM2 5005 A_23_P9

1.48 0.023091 0.056646 0.593209 0.999497 0.171531 0.999623 MATN3 4148 A_23_P1

−3.17 0.023056 0.056646 0.897744 0.999497 0.944137 0.999623 RNF216 54476 A_24_P2

2.64 0.022954 0.056646 0.399745 0.999497 0.961986 0.999623 CP110 9738 A_24_P3

−1.8 0.023131 0.056646 0.422223 0.999497 0.281232 0.999623 ATP2A2 488 A_24_P7

−2.67 0.023137 0.056646 0.914603 0.999497 0.625231 0.999623 ICK 22858 A_23_P3

−1.33 0.022649 0.056646 0.40055 0.999497 0.663226 0.999623 ELMO1 9844 A_23_P1

1.22 0.02263 0.056646 0.408629 0.999497 0.935388 0.999623 CLPTM1L 81037 A_32_P1

1.84 0.023171 0.056646 0.856714 0.999497 0.241929 0.999623 GLRX2 51022 A_23_P1

−1.33 0.023121 0.056646 0.904378 0.999497 0.293382 0.999623 RUNX3 864 A_23_P5

−1.2 0.022822 0.056646 0.742994 0.999497 0.58824 0.999623 VCP 7415 A_23_P8

1.46 0.022818 0.056646 0.736891 0.999497 0.715977 0.999623 LOC645166 645166 A_32_P2

1.25 0.022817 0.056646 0.15421 0.999497 0.685198 0.999623 PRKCDBP 112464 A_23_P2

2.92 0.022754 0.056646 0.405562 0.999497 0.190765 0.999623 RAC2 5880 A_23_P2

1.39 0.023173 0.056646 0.440046 0.999497 0.937421 0.999623 ILF2 3608 A_23_P2

1.8 0.022875 0.056646 0.556435 0.999497 0.867959 0.999623 DBN1 1627 A_24_P9

1.81 0.022907 0.056646 0.889694 0.999497 0.669193 0.999623 NFKBIL2 4796 A_23_P2

1.58 0.022988 0.056646 0.858402 0.999497 0.269339 0.999623 NFE2L1 4779 A_23_P7

1.54 0.023301 0.056759 0.855912 0.999497 0.650591 0.999623 PCDH1 5097 A_23_P2

1.53 0.023351 0.056759 0.751946 0.999497 0.205484 0.999623 CEACAM7 1087 A_24_P2

1.35 0.023344 0.056759 0.21966 0.999497 0.269926 0.999623 TAF8 129685 A_23_P1

1.31 0.023253 0.056759 0.835292 0.999497 0.422309 0.999623 FASTK 10922 A_23_P2

1.73 0.023404 0.056806 0.863451 0.999497 0.740462 0.999623 STAT5A 6776 A_24_P1

1.83 0.023464 0.056872 0.602291 0.999497 0.704537 0.999623 PPM1D 8493 A_32_P1

1.13 0.023563 0.056876 0.662459 0.999497 0.92021 0.999623 TLN2 83660 A_24_P3

1.29 0.023582 0.056876 0.134377 0.999497 0.241966 0.999623 APOA4 337 A_23_P8

1.47 0.023597 0.056876 0.826018 0.999497 0.23829 0.999623 IGF2 3481 A_23_P4

1.9 0.023596 0.056876 0.367862 0.999497 0.560618 0.999623 EDA 1896 A_23_P3

1.39 0.023641 0.056901 0.810786 0.999497 0.664527 0.999623 TNFRSF25 8718 A_23_P1

1.41 0.023674 0.056902 0.440383 0.999497 0.327934 0.999623 TPT1 7178 A_24_P3

−2.01 0.024225 0.057014 0.989532 0.999497 0.763209 0.999623 EXOC6 54536 A_23_P1

1.27 0.02423 0.057014 0.090174 0.999497 0.834501 0.999623 TAX1BP3 30851 A_23_P3

1.74 0.023911 0.057014 0.632985 0.999497 0.689932 0.999623 SHISA5 51246 A_23_P2

−1.36 0.023864 0.057014 0.666164 0.999497 0.623782 0.999623 NME2 4831 A_23_P1

−1.65 0.02417 0.057014 0.575399 0.999497 0.259454 0.999623 PPIL2 23759 A_24_P9

−2.02 0.024157 0.057014 0.666113 0.999497 0.369511 0.999623 IGJ 3512 A_23_P1

−1.38 0.023992 0.057014 0.537089 0.999497 0.514473 0.999623 FCHO2 115548 A_23_P3

−1.6 0.023998 0.057014 0.696781 0.999497 0.197378 0.999623 CAPN10 11132 A_23_P3

−5.87 0.023902 0.057014 0.397217 0.999497 0.886854 0.999623 NHEJ1 79840 A_24_P2

−1.68 0.023847 0.057014 0.69479 0.999497 0.90056 0.999623 GREM2 64388 A_23_P9

−1.48 0.023944 0.057014 0.858879 0.999497 0.551297 0.999623 PML 5371 A_23_P3

1.74 0.024224 0.057014 0.994814 0.999497 0.683126 0.999623 CTSK 1513 A_23_P3

1.42 0.024268 0.057014 0.731985 0.999497 0.504504 0.999623 PPIL2 23759 A_24_P2

1.85 0.024349 0.057014 0.814733 0.999497 0.900514 0.999623 IFT122 55764 A_23_P2

1.45 0.024348 0.057014 0.738761 0.999497 0.848825 0.999623 MAEA 10296 A_23_P1

−1.52 0.024173 0.057014 0.791352 0.999497 0.275621 0.999623 DLL3 10683 A_24_P5

1.48 0.023761 0.057014 0.317412 0.999497 0.865777 0.999623 CTNNA1 1495 A_24_P8

1.68 0.024278 0.057014 0.961889 0.999497 0.590684 0.999623 XRCC1 7515 A_23_P1

1.72 0.024315 0.057014 0.415487 0.999497 0.941061 0.999623 BAT5 7920 A_23_P1

1.79 0.024507 0.057306 0.406512 0.999497 0.268181 0.999623 GSR 2936 A_23_P1

1.43 0.024587 0.057414 0.447782 0.999497 0.402011 0.999623 CSNK2B 1460 A_24_P9

1.41 0.024627 0.05743 0.872929 0.999497 0.423811 0.999623 IL1RN 3557 A_23_P2

1.26 0.024757 0.057565 0.325441 0.999497 0.662672 0.999623 ELMO2 63916 A_24_P3

2.07 0.024782 0.057565 0.608839 0.999497 0.153068 0.999623 XRCC6 2547 A_32_P2

1.2 0.024785 0.057565 0.653775 0.999497 0.046736 0.999623 TP63 8626 A_23_P3

1.31 0.024828 0.057588 0.359601 0.999497 0.427082 0.999623 UACA 55075 A_23_P3

−2.36 0.024868 0.057601 0.96785 0.999497 0.599824 0.999623 CD1B 910 A_23_P3

1.25 0.024905 0.05761 0.838072 0.999497 0.64236 0.999623 TIRAP 114609 A_23_P2

1.45 0.024995 0.057741 0.623572 0.999497 0.353426 0.999623 C8A 731 A_23_P4

1.39 0.025118 0.057856 0.338603 0.999497 0.088464 0.999623 IFI27L1 122509 A_23_P5

1.55 0.025112 0.057856 0.915004 0.999497 0.643707 0.999623 CDKN1B 1027 A_23_P2

1.57 0.025145 0.057856 0.311175 0.999497 0.756093 0.999623 APOA4 337 A_24_P2

−1.41 0.025181 0.057862 0.53623 0.999497 0.197791 0.999623 FKBPL 63943 A_23_P7

1.53 0.025326 0.057892 0.560314 0.999497 0.128645 0.999623 SERPINB9 5272 A_24_P2

−1.65 0.025329 0.057892 0.568829 0.999497 0.58219 0.999623 COL6A2 1292 A_32_P2

1.46 0.025261 0.057892 0.872014 0.999497 0.418784 0.999623 TSLP 85480 A_23_P1

1.23 0.02532 0.057892 0.147663 0.999497 0.78859 0.999623 KRAS 3845 A_23_P3

−1.81 0.025434 0.057925 0.350719 0.999497 0.395689 0.999623 APAF1 317 A_23_P3

−1.98 0.025489 0.057925 0.284157 0.999497 0.889888 0.999623 VSIG2 23584 A_23_P3

−1.31 0.025512 0.057925 0.857542 0.999497 0.311081 0.999623 COL13A1 1305 A_24_P9

−1.33 0.0255 0.057925 0.451096 0.999497 0.824942 0.999623 TPD52 7163 A_23_P2

−1.85 0.025495 0.057925 0.84194 0.999497 0.600095 0.999623 GHSR 2693 A_23_P1

−1.83 0.025652 0.058091 0.655901 0.999497 0.755184 0.999623 COL15A1 1306 A_23_P1

−1.52 0.02565 0.058091 0.381867 0.999497 0.461919 0.999623 GNA13 10672 A_24_P9

−2.38 0.025698 0.058119 0.708494 0.999497 0.176524 0.999623 PRKCB 5579 A_23_P4

−1.39 0.02578 0.058161 0.19234 0.999497 0.531901 0.999623 DCTN3 11258 A_24_P2

1.59 0.025784 0.058161 0.526632 0.999497 0.357129 0.999623 CKAP2 26586 A_23_P1

−1.36 0.025879 0.058196 0.603597 0.999497 0.885128 0.999623 ULBP2 80328 A_23_P1

1.47 0.025877 0.058196 0.716694 0.999497 0.949984 0.999623 PAFAH1B3 5050 A_23_P1

1.33 0.025901 0.058196 0.765951 0.999497 0.813546 0.999623 CD248 57124 A_23_P5

1.52 0.025939 0.058205 0.740171 0.999497 0.263471 0.999623 ATP2A2 488 A_23_P5

1.45 0.025984 0.058231 0.855788 0.999497 0.825546 0.999623 CFLAR 8837 A_23_P2

−1.4 0.026045 0.058288 0.395349 0.999497 0.96893 0.999623 PSMF1 9491 A_23_P7

−1.34 0.026111 0.058288 0.349748 0.999497 0.867932 0.999623 FBLIM1 54751 A_23_P2

1.37 0.026085 0.058288 0.122642 0.999497 0.2457 0.999623 TUSC4 10641 A_23_P1

1.48 0.026168 0.058339 0.40297 0.999497 0.075194 0.999623 SART3 9733 A_23_P8

1.57 0.026244 0.058434 0.933546 0.999497 0.69472 0.999623 ITFG2 55846 A_23_P2

1.99 0.026393 0.058689 0.727136 0.999497 0.651347 0.999623 CSF2RB 1439 A_23_P1

1.47 0.026635 0.059 0.786508 0.999497 0.977127 0.999623 ADAM22 53616 A_24_P2

1.25 0.026632 0.059 0.431297 0.999497 0.690916 0.999623 RACGAP1 29127 A_23_P6

−1.86 0.026629 0.059 0.398668 0.999497 0.839477 0.999623 RRAGC 64121 A_23_P9

−1.71 0.026678 0.059018 0.188304 0.999497 0.043924 0.999623 ZFR2 23217 A_23_P3

1.38 0.026762 0.059052 0.222351 0.999497 0.435681 0.999623 BCL7A 605 A_32_P7

1.51 0.026748 0.059052 0.75426 0.999497 0.516311 0.999623 SNPH 9751 A_23_P1

1.43 0.027005 0.059512 0.744087 0.999497 0.358138 0.999623 EXOC2 55770 A_23_P2

1.16 0.027117 0.059532 0.182019 0.999497 0.422793 0.999623 FANCG 2189 A_23_P7

1.63 0.027117 0.059532 0.67724 0.999497 0.863808 0.999623 LTBP2 4053 A_24_P1

1.62 0.027107 0.059532 0.918361 0.999497 0.34478 0.999623 VEZF1 7716 A_24_P9

−3.39 0.027161 0.059551 0.2347 0.999497 0.459209 0.999623 BCAP31 10134 A_32_P4

1.3 0.0272 0.059561 0.828339 0.999497 0.814044 0.999623 TYK2 7297 A_23_P1

1.61 0.02731 0.059651 0.718789 0.999497 0.305446 0.999623 DNAJB6 10049 A_24_P6

−2.94 0.027306 0.059651 0.768725 0.999497 0.601868 0.999623 PRSS2 5645 A_32_P9

1.48 0.027445 0.059718 0.254523 0.999497 0.123377 0.999623 ATP2A1 487 A_23_P7

1.33 0.027434 0.059718 0.390992 0.999497 0.439009 0.999623 BBS7 55212 A_23_P2

1.26 0.027395 0.059718 0.679015 0.999497 0.781101 0.999623 KLRC2 3822 A_23_P2

−1.96 0.027513 0.05979 0.523282 0.999497 0.263981 0.999623 VPS45 11311 A_23_P2

1.57 0.027561 0.059821 0.486518 0.999497 0.948904 0.999623 PLDN 26258 A_23_P2

−2.14 0.027632 0.059822 0.271162 0.999497 0.807566 0.999623 MLL2 8085 A_24_P2

−1.5 0.027605 0.059822 0.925297 0.999497 0.438707 0.999623 UTP11L 51118 A_23_P1

−1.65 0.027951 0.060438 0.712349 0.999497 0.341129 0.999623 WDR92 116143 A_32_P1

1.35 0.028014 0.060499 0.959143 0.999497 0.631753 0.999623 LY6E 4061 A_24_P3

1.67 0.028104 0.06054 0.639579 0.999497 0.801153 0.999623 SPG7 6687 A_24_P2

1.32 0.028103 0.06054 0.815515 0.999497 0.187053 0.999623 SBDS 51119 A_23_P7

−1.81 0.028224 0.060572 0.637322 0.999497 0.855503 0.999623 PTX3 5806 A_23_P1

−1.54 0.028185 0.060572 0.545358 0.999497 0.666942 0.999623 ACVRL1 94 A_24_P9

1.28 0.028223 0.060572 0.399627 0.999497 0.675879 0.999623 MLL3 58508 A_32_P2

1.26 0.028549 0.060651 0.55675 0.999497 0.778025 0.999623 CCR10 2826 A_23_P1

1.65 0.028465 0.060651 0.753723 0.999497 0.189758 0.999623 PTPN12 5782 A_23_P8

−1.71 0.028409 0.060651 0.672264 0.999497 0.445015 0.999623 POSTN 10631 A_24_P3

−1.6 0.028613 0.060651 0.648284 0.999497 0.020574 0.999623 GPR126 57211 A_23_P2

1.13 0.028563 0.060651 0.132732 0.999497 0.306654 0.999623 SEMA3B 7869 A_24_P2

1.65 0.028588 0.060651 0.551926 0.999497 0.365382 0.999623 BIRC3 330 A_23_P9

−1.39 0.028389 0.060651 0.273709 0.999497 0.675393 0.999623 CUL5 8065 A_23_P2

−1.59 0.028487 0.060651 0.69055 0.999497 0.612001 0.999623 TOPORS 10210 A_23_P3

−1.36 0.02849 0.060651 0.561509 0.999497 0.941162 0.999623 FAF1 11124 A_23_P9

1.17 0.028357 0.060651 0.814361 0.999497 0.964896 0.999623 MLF2 8079 A_23_P1

1.35 0.028813 0.060753 0.542433 0.999497 0.705194 0.999623 IGSF1 3547 A_23_P1

1.47 0.028819 0.060753 0.842061 0.999497 0.602729 0.999623 SCARB1 949 A_23_P2

1.36 0.028837 0.060753 0.945806 0.999497 0.666927 0.999623 KLF10 7071 A_23_P1

−2.07 0.02879 0.060753 0.957562 0.999497 0.434456 0.999623 CBR1 873 A_23_P2

−1.65 0.028769 0.060753 0.302828 0.999497 0.13344 0.999623 RAB5C 5878 A_23_P1

1.36 0.028886 0.060781 0.398687 0.999497 0.499714 0.999623 TNFRSF13B 23495 A_23_P8

1.5 0.028959 0.060839 0.468352 0.999497 0.202085 0.999623 PTGS1 5742 A_23_P2

1.59 0.028984 0.060839 0.850501 0.999497 0.911628 0.999623 RHCE 6006 A_23_P6

−1.28 0.029031 0.060864 0.372412 0.999497 0.659916 0.999623 BBC3 27113 A_24_P3

1.42 0.02926 0.061195 0.922857 0.999497 0.755122 0.999623 TXLNA 200081 A_32_P8

1.48 0.029249 0.061195 0.719249 0.999497 0.62894 0.999623 FEZ1 9638 A_23_P2

1.3 0.029481 0.061583 0.302527 0.999497 0.741929 0.999623 IL27RA 9466 A_23_P2

1.47 0.029555 0.061663 0.096732 0.999497 0.219257 0.999623 PCDHB5 26167 A_23_P6

−1.28 0.029601 0.061683 0.519939 0.999497 0.243401 0.999623 MLLT4 4301 A_23_P2

1.36 0.029685 0.061784 0.292715 0.999497 0.339077 0.999623 HSPD1 3329 A_32_P7

−3.09 0.029737 0.061817 0.515284 0.999497 0.494684 0.999623 MRC2 9902 A_23_P4

1.82 0.029815 0.061906 0.428232 0.999497 0.834295 0.999623 PPP2R1A 5518 A_23_P1

1.52 0.029953 0.062117 0.912085 0.999497 0.216815 0.999623 TCF3 6929 A_23_P6

1.55 0.030032 0.062206 0.51389 0.999497 0.401865 0.999623 MAPK8 5599 A_23_P3

1.45 0.030224 0.062529 0.869519 0.999497 0.374373 0.999623 SYTL1 84958 A_32_P2

1.58 0.030264 0.062537 0.999751 0.999957 0.236159 0.999623 TNFRSF1A 7132 A_23_P1

−2.64 0.030305 0.062546 0.650778 0.999497 0.384675 0.999623 TLR9 54106 A_23_P1

1.57 0.030412 0.06261 0.804853 0.999497 0.838006 0.999623 LAMC2 3918 A_23_P2

1.28 0.030445 0.06261 0.947975 0.999497 0.332588 0.999623 ERC1 23085 A_24_P2

1.23 0.030398 0.06261 0.486291 0.999497 0.561453 0.999623 PRKCA 5578 A_23_P5

1.41 0.030626 0.062682 0.763036 0.999497 0.313272 0.999623 MSH3 4437 A_23_P1

−1.28 0.030547 0.062682 0.245368 0.999497 0.945702 0.999623 5-Sep 5413 A_24_P2

1.55 0.030596 0.062682 0.715949 0.999497 0.459014 0.999623 NDUFA13 51079 A_23_P1

1.6 0.030558 0.062682 0.782875 0.999497 0.274226 0.999623 CYFIP2 26999 A_23_P1

1.66 0.030695 0.06275 0.368667 0.999497 0.634073 0.999623 BID 637 A_23_P1

1.85 0.030794 0.062877 0.661313 0.999497 0.84687 0.999623 PARVA 55742 A_23_P4

1.25 0.030877 0.062897 0.959506 0.999497 0.920002 0.999623 MAGED1 9500 A_24_P3

1.29 0.030857 0.062897 0.369865 0.999497 0.287833 0.999623 RAB18 22931 A_23_P1

1.19 0.031017 0.063095 0.577327 0.999497 0.285604 0.999623 CDKN1A 1026 A_24_P8

1.49 0.031197 0.063095 0.788278 0.999497 0.200461 0.999623 CEBPA 1050 A_24_P2

1.5 0.031126 0.063095 0.306921 0.999497 0.188434 0.999623 ADAM33 80332 A_23_P2

1.55 0.031097 0.063095 0.485134 0.999497 0.592091 0.999623 MYBPC3 4607 A_23_P1

−2.51 0.03123 0.063095 0.456002 0.999497 0.385035 0.999623 CCL4 6351 A_23_P2

−2.79 0.031197 0.063095 0.360911 0.999497 0.22704 0.999623 IL21R 50615 A_24_P2

1.39 0.031176 0.063095 0.765221 0.999497 0.826481 0.999623 CYBA 1535 A_23_P1

1.48 0.031498 0.063104 0.820061 0.999497 0.40144 0.999623 CHRNB2 1141 A_23_P3

1.49 0.031385 0.063104 0.585591 0.999497 0.645168 0.999623 TNNC2 7125 A_23_P1

1.45 0.031527 0.063104 0.945366 0.999497 0.610019 0.999623 TFPT 29844 A_23_P2

1.53 0.03146 0.063104 0.883172 0.999497 0.350379 0.999623 EHD2 30846 A_24_P1

1.5 0.031355 0.063104 0.993684 0.999497 0.734683 0.999623 CDH18 1016 A_23_P8

1.29 0.031368 0.063104 0.828265 0.999497 0.679675 0.999623 LTBP3 4054 A_24_P2

1.53 0.031475 0.063104 0.902998 0.999497 0.95695 0.999623 CD63 967 A_23_P1

1.5 0.031524 0.063104 0.441376 0.999497 0.107585 0.999623 EIF5A 1984 A_24_P3

1.55 0.031679 0.063261 0.263799 0.999497 0.594688 0.999623 AEBP1 165 A_23_P1

1.46 0.031645 0.063261 0.442664 0.999497 0.395607 0.999623 LENG1 79165 A_23_P2

1.47 0.031818 0.063414 0.646664 0.999497 0.933681 0.999623 SIRT6 51548 A_23_P2

1.34 0.031903 0.063414 0.522245 0.999497 0.421646 0.999623 AP1S1 1174 A_24_P6

1.3 0.031872 0.063414 0.711261 0.999497 0.504707 0.999623 TIMP2 7077 A_23_P1

1.54 0.031872 0.063414 0.882487 0.999497 0.207987 0.999623 GULP1 51454 A_23_P3

−1.93 0.031986 0.063433 0.689299 0.999497 0.543041 0.999623 DAPK1 1612 A_23_P2

1.29 0.031953 0.063433 0.505182 0.999497 0.564311 0.999623 SFRS17A 8227 A_23_P3

1.25 0.032068 0.063445 0.082378 0.999497 0.492234 0.999623 PRKAR2B 5577 A_23_P4

−2.2 0.032103 0.063445 0.7629 0.999497 0.300333 0.999623 PSMA1 5682 A_23_P1

−1.37 0.032058 0.063445 0.299438 0.999497 0.527897 0.999623 LEPR 3953 A_24_P2

−1.96 0.032218 0.063527 0.785813 0.999497 0.410247 0.999623 MYBPC2 4606 A_23_P1

1.43 0.032212 0.063527 0.949079 0.999497 0.137534 0.999623 NPM1 4869 A_32_P4

−1.94 0.032263 0.063534 0.902419 0.999497 0.467736 0.999623 CCND3 896 A_23_P2

1.52 0.032295 0.063534 0.878017 0.999497 0.72382 0.999623 THOC5 8563 A_23_P1

1.29 0.032341 0.063551 0.962271 0.999497 0.941392 0.999623 ALDH1A3 220 A_23_P2

−1.32 0.032482 0.063565 0.750488 0.999497 0.270208 0.999623 PKD1 5310 A_23_P7

1.83 0.032532 0.063565 0.408551 0.999497 0.973099 0.999623 MAF 4094 A_32_P2

1.62 0.032459 0.063565 0.794258 0.999497 0.936076 0.999623 VCP 7415 A_24_P2

1.22 0.032519 0.063565 0.346933 0.999497 0.608681 0.999623 FCRLB 127943 A_23_P3

1.73 0.032444 0.063565 0.429888 0.999497 0.416771 0.999623 CTSB 1508 A_23_P2

−1.47 0.032578 0.063581 0.488009 0.999497 0.977433 0.999623 FGB 2244 A_24_P5

1.4 0.03266 0.06367 0.497199 0.999497 0.559463 0.999623 CTSC 1075 A_24_P1

−1.61 0.033185 0.063796 0.995805 0.999497 0.615207 0.999623 BBS9 27241 A_23_P8

1.19 0.033317 0.063796 0.31653 0.999497 0.913647 0.999623 ARHGDIA 396 A_24_P1

1.51 0.033156 0.063796 0.840647 0.999497 0.773433 0.999623 FGFR3 2261 A_23_P2

1.59 0.033108 0.063796 0.881589 0.999497 0.496839 0.999623 TNFRSF21 27242 A_23_P4

1.46 0.032849 0.063796 0.278269 0.999497 0.846903 0.999623 HCFC1R1 54985 A_23_P2

1.54 0.033024 0.063796 0.748762 0.999497 0.205968 0.999623 VEGFA 7422 A_24_P1

1.71 0.032983 0.063796 0.944173 0.999497 0.703621 0.999623 HBP1 26959 A_24_P2

−1.59 0.033215 0.063796 0.798522 0.999497 0.245275 0.999623 BBS2 583 A_23_P1

1.23 0.033285 0.063796 0.1723 0.999497 0.261281 0.999623 PTGFR 5737 A_24_P3

1.25 0.033071 0.063796 0.619445 0.999497 0.938937 0.999623 NGFR 4804 A_23_P3

1.44 0.033202 0.063796 0.810191 0.999497 0.472641 0.999623 FBLIM1 54751 A_24_P9

1.48 0.032872 0.063796 0.768085 0.999497 0.76898 0.999623 ADAMTS7 11173 A_23_P3

1.33 0.033246 0.063796 0.514772 0.999497 0.250831 0.999623 SIVA1 10572 A_24_P1

1.43 0.033253 0.063796 0.825935 0.999497 0.482239 0.999623 FCGR3B 2215 A_23_P1

−3.65 0.032777 0.063796 0.504655 0.999497 0.63578 0.999623 XPA 7507 A_23_P6

1.31 0.033168 0.063796 0.973303 0.999497 0.318812 0.999623 TAPBP 6892 A_23_P3

1.35 0.033357 0.063801 0.617357 0.999497 0.52104 0.999623 COL18A1 80781 A_24_P5

2.23 0.033707 0.064009 0.369159 0.999497 0.785081 0.999623 COL20A1 57642 A_32_P1

1.32 0.03358 0.064009 0.48373 0.999497 0.239762 0.999623 RNF34 80196 A_32_P7

−1.41 0.033591 0.064009 0.916876 0.999497 0.090264 0.999623 C9orf127 51754 A_23_P2

−1.35 0.033696 0.064009 0.301834 0.999497 0.387275 0.999623 TXLNA 200081 A_23_P5

1.51 0.033687 0.064009 0.919058 0.999497 0.794959 0.999623 MALL 7851 A_24_P8

1.45 0.033716 0.064009 0.838832 0.999497 0.614491 0.999623 TBXAS1 6916 A_32_P2

1.29 0.033725 0.064009 0.476815 0.999497 0.497037 0.999623 NFATC1 4772 A_24_P2

2.31 0.033788 0.064058 0.484876 0.999497 0.188787 0.999623 TERT 7015 A_23_P1

2.15 0.033887 0.064123 0.904127 0.999497 0.891923 0.999623 ZFYVE16 9765 A_24_P2

−2.49 0.033909 0.064123 0.562591 0.999497 0.318679 0.999623 FUT3 2525 A_23_P3

1.53 0.033934 0.064123 0.875302 0.999497 0.621745 0.999623 HAPLN4 404037 A_23_P4

1.37 0.033975 0.06413 0.492467 0.999497 0.118386 0.999623 VAV1 7409 A_23_P3

1.61 0.034064 0.064213 0.380843 0.999497 0.861607 0.999623 HRK 8739 A_23_P2

1.36 0.034093 0.064213 0.54629 0.999497 0.493787 0.999623 IFI27L2 83982 A_23_P1

1.53 0.034226 0.064345 0.542263 0.999497 0.208311 0.999623 TOM1 10043 A_23_P1

1.49 0.034294 0.064345 0.422176 0.999497 0.643378 0.999623 SLPI 6590 A_24_P1

1.44 0.034284 0.064345 0.255446 0.999497 0.596129 0.999623 FKBP1A 2280 A_23_P1

1.65 0.034313 0.064345 0.355904 0.999497 0.748701 0.999623 TERF1 7013 A_32_P2

−1.78 0.034374 0.064348 0.606755 0.999497 0.565852 0.999623 IRF7 3665 A_24_P3

1.33 0.034412 0.064348 0.398343 0.999497 0.717063 0.999623 C2 717 A_32_P1

1.31 0.034427 0.064348 0.742981 0.999497 0.353564 0.999623 RRAD 6236 A_24_P2

1.41 0.03452 0.064453 0.301818 0.999497 0.626374 0.999623 ICOSLG 23308 A_23_P6

−1.56 0.034668 0.064659 0.789295 0.999497 0.107452 0.999623 EEF2 1938 A_24_P8

1.45 0.034707 0.064661 0.296008 0.999497 0.285848 0.999623 CHRNA7 1139 A_23_P1

1.55 0.034872 0.064724 0.58819 0.999497 0.408751 0.999623 SCD5 79966 A_23_P2

1.45 0.034902 0.064724 0.6819 0.999497 0.314801 0.999623 ATHL1 80162 A_23_P9

1.47 0.034966 0.064724 0.318446 0.999497 0.427014 0.999623 GCLM 2730 A_23_P1

−1.49 0.034959 0.064724 0.924876 0.999497 0.331781 0.999623 MLLT6 4302 A_32_P9

1.29 0.034953 0.064724 0.825453 0.999497 0.568063 0.999623 WWTR1 25937 A_32_P6

1.36 0.034797 0.064724 0.323648 0.999497 0.863363 0.999623 PRDX1 5052 A_23_P1

1.34 0.035081 0.064868 0.231794 0.999497 0.6463 0.999623 PXN 5829 A_23_P4

1.56 0.035123 0.064876 0.842538 0.999497 0.30583 0.999623 PRKCSH 5589 A_24_P3

1.79 0.035235 0.065012 0.531771 0.999497 0.921556 0.999623 BCLAF1 9774 A_24_P8

−1.8 0.035453 0.065255 0.846611 0.999497 0.829268 0.999623 TNFAIP8L1 126282 A_23_P4

1.56 0.035448 0.065255 0.483639 0.999497 0.701125 0.999623 BAT2L 84726 A_24_P9

1.5 0.03548 0.065255 0.301971 0.999497 0.432894 0.999623 RTKN 6242 A_23_P1

1.46 0.035523 0.065265 0.457554 0.999497 0.302307 0.999623 CTNND1 1500 A_23_P2

−1.41 0.03565 0.065286 0.7144 0.999497 0.245176 0.999623 MYST3 7994 A_23_P4

1.22 0.035735 0.065286 0.59063 0.999497 0.520196 0.999623 MLL 4297 A_24_P9

1.74 0.035679 0.065286 0.678586 0.999497 0.972241 0.999623 CSRNP1 64651 A_23_P1

1.27 0.035762 0.065286 0.224143 0.999497 0.960358 0.999623 LY6K 54742 A_32_P2

1.24 0.035583 0.065286 0.750624 0.999497 0.45165 0.999623 PLDN 26258 A_23_P2

1.21 0.035698 0.065286 0.259189 0.999497 0.033897 0.999623 IGBP1 3476 A_23_P1

−1.68 0.035812 0.065308 0.628936 0.999497 0.43381 0.999623 CLDN1 9076 A_24_P1

1.28 0.035893 0.065323 0.672177 0.999497 0.017062 0.999623 LY86 9450 A_23_P7

1.27 0.035896 0.065323 0.634683 0.999497 0.73318 0.999623 SEMA3B 7869 A_23_P1

1.19 0.035945 0.065344 0.237064 0.999497 0.408716 0.999623 IGF2BP1 10642 A_23_P8

1.4 0.036054 0.065472 0.208519 0.999497 0.335448 0.999623 FANCI 55215 A_23_P3

−2.62 0.036106 0.065499 0.475677 0.999497 0.588487 0.999623 GRN 2896 A_23_P4

1.49 0.036236 0.065559 0.410007 0.999497 0.210933 0.999623 SMOC1 64093 A_24_P1

1.54 0.036368 0.065559 0.751552 0.999497 0.588362 0.999623 CBARA1 10367 A_23_P4

−1.24 0.036358 0.065559 0.275835 0.999497 0.97784 0.999623 BGLAP 632 A_23_P1

1.54 0.036338 0.065559 0.658997 0.999497 0.331015 0.999623 AP1S2 8905 A_24_P1

−1.44 0.036294 0.065559 0.09235 0.999497 0.358259 0.999623 UACA 55075 A_24_P2

1.47 0.03622 0.065559 0.31198 0.999497 0.39171 0.999623 AATK 9625 A_23_P1

1.31 0.036427 0.065597 0.473991 0.999497 0.956776 0.999623 MAP3K5 4217 A_23_P1

−2.36 0.036467 0.065601 0.494233 0.999497 0.366173 0.999623 CD5 921 A_24_P3

1.3 0.036675 0.065905 0.814369 0.999497 0.292644 0.999623 PTK2B 2185 A_23_P1

2.03 0.037067 0.06621 0.339483 0.999497 0.265766 0.999623 SRC 6714 A_23_P3

1.35 0.037344 0.06621 0.627243 0.999497 0.955467 0.999623 IMPDH1 3614 A_24_P8

1.59 0.037174 0.06621 0.659222 0.999497 0.612172 0.999623 LIMS1 3987 A_23_P2

−1.55 0.037261 0.06621 0.629349 0.999497 0.549508 0.999623 CD4 920 A_24_P2

−2.75 0.037125 0.06621 0.966905 0.999497 0.286739 0.999623 FRAP1 2475 A_23_P3

1.46 0.037277 0.06621 0.809112 0.999497 0.566189 0.999623 HSPA1A 3303 A_24_P6

1.59 0.036909 0.06621 0.887857 0.999497 0.415038 0.999623 PRDX2 7001 A_32_P2

1.84 0.03694 0.06621 0.555601 0.999497 0.861216 0.999623 VAMP3 9341 A_23_P9

1.36 0.037161 0.06621 0.864031 0.999497 0.65595 0.999623 TOP2B 7155 A_23_P1

−1.33 0.037062 0.06621 0.941946 0.999497 0.51165 0.999623 ERCC1 2067 A_23_P1

1.35 0.037233 0.06621 0.873782 0.999497 0.66258 0.999623 PHB 5245 A_24_P2

1.17 0.037113 0.06621 0.633978 0.999497 0.067449 0.999623 YWHAZ 7534 A_32_P2

−1.43 0.037331 0.06621 0.607754 0.999497 0.720726 0.999623 UBE2N 7334 A_32_P1

−1.28 0.03743 0.066295 0.543764 0.999497 0.42914 0.999623 C8orf4 56892 A_23_P2

−1.86 0.037619 0.066561 0.725317 0.999497 0.615774 0.999623 CD97 976 A_23_P5

1.5 0.037696 0.066629 0.966568 0.999497 0.409637 0.999623 CBLB 868 A_23_P2

1.23 0.037782 0.066677 0.200474 0.999497 0.518392 0.999623 GP1BB 2812 A_23_P2

2.12 0.037967 0.066677 0.49344 0.999497 0.479874 0.999623 WWTR1 25937 A_24_P9

−1.68 0.037822 0.066677 0.866945 0.999497 0.547464 0.999623 DNASE1L3 1776 A_23_P2

1.14 0.038125 0.066677 0.317968 0.999497 0.493312 0.999623 PPP1R13B 23368 A_23_P2

1.44 0.038021 0.066677 0.546261 0.999497 0.8945 0.999623 EBI3 10148 A_23_P1

1.14 0.037841 0.066677 0.730837 0.999497 0.16421 0.999623 CEBPB 1051 A_23_P1

1.43 0.038082 0.066677 0.414807 0.999497 0.430171 0.999623 OSCAR 126014 A_23_P5

1.3 0.038096 0.066677 0.501881 0.999497 0.970502 0.999623 SGPL1 8879 A_23_P7

1.32 0.038128 0.066677 0.569951 0.999497 0.507742 0.999623 ADAM12 8038 A_23_P2

1.34 0.037935 0.066677 0.050751 0.999497 0.627833 0.999623 PDZD2 23037 A_23_P7

1.44 0.038149 0.066677 0.26995 0.999497 0.301539 0.999623 TEK 7010 A_23_P3

1.48 0.038188 0.066678 0.218137 0.999497 0.415731 0.999623 FLVCR1 28982 A_23_P1

1.33 0.038289 0.066786 0.676007 0.999497 0.815572 0.999623 PSMA3 5684 A_23_P1

−1.33 0.038396 0.066838 0.429774 0.999497 0.404923 0.999623 CSF1 1435 A_23_P4

1.19 0.038392 0.066838 0.262292 0.999497 0.194732 0.999623 CD68 968 A_23_P1

1.64 0.038438 0.066843 0.186404 0.999497 0.619938 0.999623 PCDHB7 56129 A_24_P2

1.19 0.038495 0.066853 0.903951 0.999497 0.426421 0.999623 JAG1 182 A_23_P2

−1.4 0.038521 0.066853 0.379778 0.999497 0.349641 0.999623 ELF1 1997 A_24_P7

−2.17 0.038608 0.066868 0.648052 0.999497 0.404488 0.999623 COL18A1 80781 A_23_P2

1.37 0.038572 0.066868 0.316143 0.999497 0.97801 0.999623 MSRA 4482 A_23_P6

1.27 0.038699 0.066894 0.889898 0.999497 0.940286 0.999623 FGFR1 2260 A_23_P3

1.46 0.0387 0.066894 0.912491 0.999497 0.213834 0.999623 IGF2BP2 10644 A_23_P2

1.25 0.039017 0.067051 0.205824 0.999497 0.856667 0.999623 FERMT2 10979 A_23_P8

−1.47 0.039058 0.067051 0.449805 0.999497 0.327004 0.999623 METTL1 4234 A_23_P4

1.45 0.038859 0.067051 0.816033 0.999497 0.583595 0.999623 PECR 55825 A_23_P9

1.51 0.038948 0.067051 0.884259 0.999497 0.820681 0.999623 CCRL2 9034 A_23_P6

1.28 0.039102 0.067051 0.734989 0.999497 0.392005 0.999623 ISG20 3669 A_23_P3

1.46 0.03902 0.067051 0.330731 0.999497 0.806808 0.999623 VEGFB 7423 A_24_P5

1.68 0.039039 0.067051 0.796219 0.999497 0.472839 0.999623 SMOC2 64094 A_23_P7

1.22 0.039102 0.067051 0.58029 0.999497 0.428484 0.999623 PRF1 5551 A_23_P1

−2.85 0.039259 0.067197 0.250656 0.999497 0.651678 0.999623 CALR 811 A_23_P6

1.6 0.039265 0.067197 0.331002 0.999497 0.554073 0.999623 SFN 2810 A_23_P6

1.4 0.039388 0.06734 0.756443 0.999497 0.927541 0.999623 RPH3AL 9501 A_23_P9

1.48 0.039521 0.067366 0.35573 0.999497 0.808914 0.999623 AIRE 326 A_23_P6

−1.41 0.039517 0.067366 0.619415 0.999497 0.551874 0.999623 ADORA2A 135 A_24_P2

1.68 0.03951 0.067366 0.570034 0.999497 0.813103 0.999623 MTCH1 23787 A_24_P2

1.34 0.039611 0.067394 0.45622 0.999497 0.917992 0.999623 GSG2 83903 A_23_P6

1.35 0.039615 0.067394 0.10052 0.999497 0.844113 0.999623 TM2D1 83941 A_23_P1

−2.07 0.039693 0.06746 0.872628 0.999497 0.986858 0.999623 NFATC2IP 84901 A_23_P1

1.21 0.039962 0.06785 0.31469 0.999497 0.910653 0.999623 IRF3 3661 A_23_P2

1.66 0.040046 0.067925 0.741216 0.999497 0.098662 0.999623 TGFB1 7040 A_24_P7

1.7 0.040109 0.067965 0.797209 0.999497 0.292058 0.999623 EEF1A1 1915 A_32_P4

−1.87 0.040328 0.068109 0.900192 0.999497 0.92053 0.999623 FOXP1 27086 A_24_P3

−1.58 0.040352 0.068109 0.3515 0.999497 0.899575 0.999623 CBLB 868 A_23_P2

−1.33 0.040295 0.068109 0.534774 0.999497 0.943076 0.999623 HLA-DOB 3112 A_23_P3

1.49 0.040279 0.068109 0.300797 0.999497 0.332659 0.999623 BAT4 7918 A_23_P1

1.25 0.040486 0.068269 0.351473 0.999497 0.412532 0.999623 NOSTRIN 115677 A_23_P7

1.48 0.040846 0.068541 0.163568 0.999497 0.198707 0.999623 NPM1 4869 A_24_P8

1.33 0.04083 0.068541 0.441115 0.999497 0.290941 0.999623 PCDHGA8 9708 A_23_P3

1.39 0.040769 0.068541 0.358886 0.999497 0.639883 0.999623 WISP2 8839 A_23_P1

2.1 0.040729 0.068541 0.752003 0.999497 0.762391 0.999623 SIPA1 6494 A_23_P1

1.44 0.040756 0.068541 0.753914 0.999497 0.69068 0.999623 HIVEP2 3097 A_23_P2

1.58 0.040923 0.068604 0.735097 0.999497 0.43867 0.999623 FKBP9 11328 A_23_P3

1.16 0.04097 0.068615 0.739192 0.999497 0.737438 0.999623 BTG1 694 A_32_P2

1.35 0.041055 0.068625 0.89781 0.999497 0.103594 0.999623 MAST1 22983 A_23_P1

1.34 0.041027 0.068625 0.689448 0.999497 0.320766 0.999623 SERPING1 710 A_23_P1

1.48 0.041165 0.068629 0.537946 0.999497 0.585445 0.999623 IRAK1 3654 A_23_P7

1.82 0.041217 0.068629 0.346895 0.999497 0.397119 0.999623 PTGES3 10728 A_24_P2

−1.7 0.041217 0.068629 0.400474 0.999497 0.899976 0.999623 ARHGDIA 396 A_23_P2

1.42 0.041146 0.068629 0.937183 0.999497 0.797306 0.999623 PTCD2 79810 A_24_P1

−2.25 0.041264 0.068641 0.804729 0.999497 0.312599 0.999623 CYTIP 9595 A_23_P9

−1.43 0.041387 0.068658 0.402373 0.999497 0.26584 0.999623 BIRC7 79444 A_23_P7

1.39 0.041362 0.068658 0.826231 0.999497 0.932431 0.999623 CDH4 1002 A_23_P2

1.27 0.041394 0.068658 0.984845 0.999497 0.506975 0.999623 RYBP 23429 A_23_P3

1.25 0.041476 0.068729 0.973564 0.999497 0.950795 0.999623 ABCA1 19 A_24_P2

−1.44 0.041522 0.068737 0.994963 0.999497 0.233991 0.999623 TRAF7 84231 A_24_P5

−2.6 0.041571 0.068754 0.998076 0.999497 0.560697 0.999623 DCBLD1 285761 A_23_P4

1.23 0.041836 0.068772 0.305884 0.999497 0.724295 0.999623 PSMC1 5700 A_24_P3

−1.31 0.042055 0.068772 0.799563 0.999497 0.530682 0.999623 NFASC 23114 A_24_P3

1.27 0.041644 0.068772 0.087798 0.999497 0.296733 0.999623 RAD9A 5883 A_24_P2

1.33 0.041975 0.068772 0.962305 0.999497 0.558778 0.999623 TAL2 6887 A_23_P4

1.31 0.042007 0.068772 0.264624 0.999497 0.304782 0.999623 UCP3 7352 A_23_P2

1.51 0.042132 0.068772 0.694175 0.999497 0.234801 0.999623 MAMDC2 256691 A_32_P4

1.38 0.041863 0.068772 0.79643 0.999497 0.633976 0.999623 SDF2 6388 A_23_P1

1.41 0.042031 0.068772 0.399052 0.999497 0.635088 0.999623 CD81 975 A_23_P1

1.56 0.04191 0.068772 0.419469 0.999497 0.762805 0.999623 STK17A 9263 A_24_P3

−1.64 0.042013 0.068772 0.847399 0.999497 0.358757 0.999623 AURKC 6795 A_23_P5

1.4 0.042006 0.068772 0.480049 0.999497 0.54651 0.999623 ITGA7 3679 A_23_P1

1.47 0.041848 0.068772 0.710712 0.999497 0.283288 0.999623 PSMD14 10213 A_23_P1

−1.36 0.042141 0.068772 0.458016 0.999497 0.274646 0.999623 FSCN1 6624 A_23_P1

1.5 0.042083 0.068772 0.689746 0.999497 0.849582 0.999623 MAPK9 5601 A_23_P1

−1.71 0.042221 0.068773 0.745508 0.999497 0.424412 0.999623 HSP90AA1 3320 A_32_P1

−2.34 0.042189 0.068773 0.970412 0.999497 0.777715 0.999623 ICAM4 3386 A_23_P1

1.54 0.042372 0.068887 0.865075 0.999497 0.326853 0.999623 CXCR3 2833 A_23_P1

−2.58 0.042355 0.068887 0.823285 0.999497 0.314022 0.999623 RIN2 54453 A_23_P1

1.39 0.04255 0.069112 0.172327 0.999497 0.654862 0.999623 PSEN1 5663 A_23_P2

1.37 0.042646 0.069203 0.374946 0.999497 0.988842 0.999623 SECTM1 6398 A_24_P4

−1.59 0.042703 0.06923 0.402995 0.999497 0.507383 0.999623 LYAR 55646 A_23_P4

−1.53 0.042853 0.069343 0.318999 0.999497 0.799633 0.999623 GRK5 2869 A_23_P1

1.21 0.042815 0.069343 0.325056 0.999497 0.974853 0.999623 ROM1 6094 A_23_P1

1.52 0.042908 0.069366 0.721971 0.999497 0.489213 0.999623 SH2D1A 4068 A_23_P4

−1.65 0.042988 0.069431 0.23822 0.999497 0.86803 0.999623 CLN3 1201 A24P2

1.36 0.043199 0.069433 0.609698 0.999497 0.494394 0.999623 ANGPTL4 51129 A_23_P1

1.8 0.043231 0.069433 0.562689 0.999497 0.654075 0.999623 FUT4 2526 A_23_P1

1.33 0.04319 0.069433 0.189847 0.999497 0.331627 0.999623 ENPP2 5168 A_23_P9

1.24 0.043185 0.069433 0.397435 0.999497 0.822373 0.999623 BMPR1A 657 A_24_P4

1.28 0.043121 0.069433 0.941555 0.999497 0.637727 0.999623 EI24 9538 A_24_P4

1.39 0.043099 0.069433 0.592521 0.999497 0.708771 0.999623 CROP 51747 A_24_P3

−1.85 0.043511 0.069568 0.878013 0.999497 0.49499 0.999623 SERPINA3 12 A_23_P1

1.2 0.043506 0.069568 0.194155 0.999497 0.539888 0.999623 EXOC4 60412 A_23_P1

1.14 0.043431 0.069568 0.460005 0.999497 0.739296 0.999623 PDCL3 79031 A_32_P1

−1.31 0.043597 0.069568 0.82953 0.999497 0.882722 0.999623 CDC42SE2 56990 A_23_P4

1.65 0.043592 0.069568 0.941825 0.999497 0.973747 0.999623 TGFBR2 7048 A_23_P3

1.32 0.043564 0.069568 0.445034 0.999497 0.962719 0.999623 CRYAA 1409 A_23_P3

1.3 0.043526 0.069568 0.977503 0.999497 0.456865 0.999623 ATL1 51062 A_23_P8

1.33 0.043673 0.069624 0.350602 0.999497 0.46682 0.999623 MZF1 7593 A_23_P1

1.51 0.0439 0.06992 0.688516 0.999497 0.935398 0.999623 FNDC3A 22862 A_23_P2

−2.64 0.044282 0.070403 0.592107 0.999497 0.609437 0.999623 CDC2L2 728642 A_24_P9

1.55 0.044284 0.070403 0.861503 0.999497 0.991662 0.999623 3-Mar 115123 A_23_P3

1.32 0.044347 0.070438 0.293459 0.999497 0.650932 0.999623 SIRPA 140885 A_24_P2

1.44 0.044492 0.07055 0.560109 0.999497 0.249875 0.999623 PTPRF 5792 A_24_P3

−1.32 0.0445 0.07055 0.454858 0.999497 0.764493 0.999623 GSTP1 2950 A_23_P2

1.39 0.044573 0.070602 0.828026 0.999497 0.13349 0.999623 FKBP1A 2280 A_32_P5

−1.53 0.044868 0.070777 0.65713 0.999497 0.745111 0.999623 PCNA 5111 A_23_P2

−1.51 0.045095 0.070777 0.728671 0.999497 0.361769 0.999623 ATF2 1386 A_24_P2

1.32 0.045028 0.070777 0.69581 0.999497 0.63401 0.999623 MNT 4335 A_24_P3

−1.72 0.045044 0.070777 0.382325 0.999497 0.327378 0.999623 ATP5O 539 A_23_P1

1.31 0.044989 0.070777 0.171139 0.999497 0.592729 0.999623 APIP 51074 A_23_P2

−1.43 0.045078 0.070777 0.129824 0.999497 0.3636 0.999623 CD36 948 A_23_P1

1.41 0.044796 0.070777 0.969281 0.999497 0.152155 0.999623 NME5 8382 A_23_P1

1.3 0.045049 0.070777 0.500561 0.999497 0.34537 0.999623 HCG18 414777 A_24_P5

1.43 0.044934 0.070777 0.879112 0.999497 0.293233 0.999623 MUC4 4585 A_24_P2

1.63 0.044783 0.070777 0.742799 0.999497 0.495826 0.999623 PDGFRL 5157 A_23_P6

−1.44 0.045146 0.070794 0.615637 0.999497 0.330274 0.999623 TOLLIP 54472 A_24_P2

−1.71 0.045435 0.071067 0.933862 0.999497 0.453475 0.999623 GNL1 2794 A_23_P1

1.5 0.045377 0.071067 0.949038 0.999497 0.420492 0.999623 DGCR8 54487 A_23_P2

1.48 0.045444 0.071067 0.466895 0.999497 0.44656 0.999623 PPFIBP1 8496 A_23_P3

−3.99 0.045722 0.071192 0.813694 0.999497 0.676853 0.999623 TXN 7295 A_24_P1

−1.35 0.045731 0.071192 0.527585 0.999497 0.140613 0.999623 OPA1 4976 A_23_P2

1.3 0.045702 0.071192 0.968662 0.999497 0.768005 0.999623 SOCS1 8651 A_24_P4

1.31 0.045645 0.071192 0.619718 0.999497 0.206638 0.999623 ALG9 79796 A_32_P4

1.62 0.045727 0.071192 0.255926 0.999497 0.353473 0.999623 CUL5 8065 A_32_P1

1.2 0.045806 0.071244 0.386454 0.999497 0.95481 0.999623 IKBKAP 8518 A_23_P1

−1.91 0.045952 0.071388 0.954821 0.999497 0.806443 0.999623 DDX41 51428 A_23_P1

1.31 0.045981 0.071388 0.843995 0.999497 0.810098 0.999623 PIWIL2 55124 A_23_P2

1.33 0.046063 0.071429 0.826224 0.999497 0.283979 0.999623 COL6A1 1291 A_24_P5

1.41 0.04609 0.071429 0.903557 0.999497 0.13481 0.999623 PRKRIR 5612 A_23_P2

1.21 0.04619 0.07152 0.215995 0.999497 0.415878 0.999623 ASGR1 432 A_23_P1

1.4 0.046274 0.071585 0.328991 0.999497 0.511678 0.999623 SIRPA 140885 A_23_P2

1.53 0.046507 0.071762 0.666027 0.999497 0.589137 0.999623 SHFM1 7979 A_23_P4

−1.37 0.046459 0.071762 0.515968 0.999497 0.69132 0.999623 PCDHGA3 56112 A_24_P3

1.25 0.046513 0.071762 0.258594 0.999497 0.137665 0.999623 SCYE1 9255 A_23_P1

−1.56 0.04672 0.071766 0.812198 0.999497 0.315334 0.999623 MYC 4609 A_24_P1

−1.59 0.046802 0.071766 0.977739 0.999497 0.296596 0.999623 IL17RA 23765 A_23_P1

1.32 0.046815 0.071766 0.371759 0.999497 0.118861 0.999623 PAGE1 8712 A_24_P3

1.16 0.046785 0.071766 0.935663 0.999497 0.550923 0.999623 ZAK 51776 A_23_P3

−1.44 0.046667 0.071766 0.777675 0.999497 0.567119 0.999623 CALM3 808 A_24_P2

1.5 0.04675 0.071766 0.811511 0.999497 0.194461 0.999623 CD55 1604 A_24_P1

−1.26 0.046892 0.071766 0.259449 0.999497 0.884425 0.999623 H2AFX 3014 A_24_P3

1.36 0.046959 0.071766 0.095474 0.999497 0.293479 0.999623 CP110 9738 A_23_P2

−1.72 0.04697 0.071766 0.549938 0.999497 0.930941 0.999623 ITGA9 3680 A_24_P6

1.31 0.046745 0.071766 0.221123 0.999497 0.285706 0.999623 DNM2 1785 A_23_P4

1.61 0.046974 0.071766 0.952938 0.999497 0.614731 0.999623 CD96 10225 A_23_P4

1.25 0.047027 0.071784 0.20498 0.999497 0.086648 0.999623 TNIP2 79155 A_23_P2

1.45 0.047183 0.071939 0.655112 0.999497 0.999335 0.999623 ALG1 56052 A_32_P1

1.3 0.047213 0.071939 0.572971 0.999497 0.61471 0.999623 SCYE1 9255 A_24_P3

−1.68 0.047277 0.071973 0.766268 0.999497 0.57458 0.999623 MCL1 4170 A_24_P3

−2.16 0.047418 0.072053 0.889888 0.999497 0.381535 0.999623 PRKAR1A 5573 A_24_P3

−1.64 0.047401 0.072053 0.511529 0.999497 0.177114 0.999623 IGF2BP3 10643 A_23_P1

1.26 0.047454 0.072053 0.591045 0.999497 0.864679 0.999623 MLH1 4292 A_23_P6

−1.63 0.047976 0.072653 0.630992 0.999497 0.122333 0.999623 FLRT3 23767 A_23_P1

1.37 0.047953 0.072653 0.838091 0.999497 0.790526 0.999623 PBX1 5087 A_23_P6

1.33 0.047962 0.072653 0.359381 0.999497 0.59874 0.999623 RELA 5970 A_23_P1

1.49 0.048214 0.072949 0.73911 0.999497 0.263018 0.999623 FOXC1 2296 A_32_P2

−1.56 0.048476 0.073281 0.387431 0.999497 0.900154 0.999623 MLLT1 4298 A_23_P1

1.52 0.048922 0.073693 0.648386 0.999497 0.211593 0.999623 PDIA3 2923 A_32_P6

−1.79 0.049133 0.073693 0.20452 0.999497 0.609904 0.999623 CYCS 54205 A_32_P1

1.48 0.049129 0.073693 0.639667 0.999497 0.26236 0.999623 NFE2L2 4780 A_24_P9

1.32 0.049107 0.073693 0.266244 0.999497 0.239128 0.999623 HTATSF1 27336 A_23_P4

−1.49 0.048971 0.073693 0.359184 0.999497 0.214235 0.999623 TRIB3 57761 A_23_P2

1.48 0.048901 0.073693 0.970463 0.999497 0.565315 0.999623 FOXP1 27086 A_23_P1

−1.19 0.048856 0.073693 0.732264 0.999497 0.857483 0.999623 ADAM11 4185 A_23_P5

−1.3 0.049132 0.073693 0.710373 0.999497 0.858642 0.999623 CCL28 56477 A_23_P5

−1.49 0.04885 0.073693 0.585233 0.999497 0.981947 0.999623 PPM1F 9647 A_24_P1

1.54 0.049182 0.073702 0.605032 0.999497 0.477826 0.999623 TIMP3 7078 A_23_P3

1.64 0.049266 0.073763 0.465532 0.999497 0.707186 0.999623 F7 2155 A_23_P1

1.39 0.049347 0.073821 0.59254 0.999497 0.236397 0.999623 COPG 22820 A_23_P4

1.24 0.049474 0.073946 0.858751 0.999497 0.54968 0.999623 PDIA3 2923 A_24_P1

−1.31 0.049589 0.074054 0.522978 0.999497 0.684458 0.999623 PTPN11 5781 A_23_P9

1.46 0.049759 0.074116 0.711278 0.999497 0.902129 0.999623 CX3CL1 6376 A_24_P3

1.58 0.049724 0.074116 0.934763 0.999497 0.728325 0.999623 IL6ST 3572 A_23_P5

1.36 0.049726 0.074116 0.821297 0.999497 0.75394 0.999623 MPZL3 196264 A_24_P2

−1.49 0.049947 0.074236 0.804556 0.999497 0.184604 0.999623 PCDHB8 56128 A_23_P4

1.33 0.049969 0.074236 0.987622 0.999497 0.506273 0.999623 DLG5 9231 A_24_P1

−1.79 0.0499 0.074236 0.744695 0.999497 0.188498 0.999623 CDH23 64072 A_24_P9

1.53 0.05054 0.074955 0.938805 0.999497 0.522084 0.999623 BCL2 596 A_23_P3

−1.75 0.050506 0.074955 0.490873 0.999497 0.477736 0.999623 ICA1 3382 A_24_P3

1.45 0.050587 0.07496 0.828191 0.999497 0.836975 0.999623 ITGB3BP 23421 A_23_P2

1.35 0.050776 0.075175 0.500913 0.999497 0.901291 0.999623 MAPK11 5600 A_23_P5

1.6 0.050917 0.075319 0.626765 0.999497 0.385447 0.999623 CDKN2C 1031 A_23_P8

1.33 0.051088 0.075378 0.50526 0.999497 0.343098 0.999623 DOCK4 9732 A_23_P5

−1.98 0.051014 0.075378 0.929724 0.999497 0.373991 0.999623 KIAA0368 23392 A_23_P1

−1.4 0.051049 0.075378 0.47502 0.999497 0.675111 0.999623 CLN3 1201 A_32_P5

−1.47 0.051216 0.075502 0.916349 0.999497 0.984168 0.999623 ADAM15 8751 A_23_P1

1.45 0.051276 0.075526 0.519439 0.999497 0.246545 0.999623 EDN1 1906 A_23_P2

1.37 0.051411 0.075661 0.803693 0.999497 0.664785 0.999623 FCGBP 8857 A_32_P2

−1.73 0.051757 0.075976 0.704005 0.999497 0.552795 0.999623 BICD2 23299 A_24_P4

1.17 0.05175 0.075976 0.510926 0.999497 0.715863 0.999623 IRF7 3665 A_24_P1

1.39 0.051675 0.075976 0.818667 0.999497 0.179341 0.999623 NOXA1 10811 A_23_P2

1.56 0.051885 0.076078 0.936563 0.999497 0.606702 0.999623 GALNTL1 57452 A_23_P7

1.58 0.05192 0.076078 0.480342 0.999497 0.736755 0.999623 BBS4 585 A_24_P1

1.31 0.051959 0.076078 0.993054 0.999497 0.954196 0.999623 FOXO1 2308 A_23_P1

−1.21 0.052208 0.076378 0.227461 0.999497 0.914728 0.999623 PPP1CA 5499 A_23_P4

1.44 0.052271 0.076404 0.988265 0.999497 0.198388 0.999623 LIN7C 55327 A_24_P1

1.28 0.052533 0.076625 0.498493 0.999497 0.671202 0.999623 ADRM1 11047 A_24_P3

1.6 0.052555 0.076625 0.945303 0.999497 0.776911 0.999623 SRF 6722 A_24_P3

1.3 0.05255 0.076625 0.527336 0.999497 0.744148 0.999623 SSX2IP 117178 A_23_P2

−1.6 0.052655 0.076657 0.974178 0.999497 0.789061 0.999623 LAX1 54900 A_24_P2

−1.95 0.052666 0.076657 0.487883 0.999497 0.422744 0.999623 ZNF503 84858 A_23_P2

1.44 0.052814 0.076807 0.728954 0.999497 0.466738 0.999623 PTK7 5754 A_24_P3

1.35 0.052966 0.076963 0.910405 0.999497 0.232492 0.999623 RAB5A 5868 A_24_P2

−1.23 0.053024 0.076982 0.566482 0.999497 0.295912 0.999623 CYBB 1536 A_24_P3

−1.79 0.053283 0.077294 0.688119 0.999497 0.312165 0.999623 YARS 8565 A_23_P3

1.74 0.054031 0.077326 0.821487 0.999497 0.494963 0.999623 MUC5AC 4586 A_24_P9

1.94 0.05393 0.077326 0.232507 0.999497 0.2196 0.999623 CNTROB 116840 A_23_P9

1.66 0.05389 0.077326 0.91235 0.999497 0.439556 0.999623 PHF17 79960 A_23_P1

1.34 0.053962 0.077326 0.494722 0.999497 0.250703 0.999623 ADRM1 11047 A_23_P6

1.59 0.053526 0.077326 0.70912 0.999497 0.521504 0.999623 C2CD2L 9854 A_23_P3

1.43 0.053976 0.077326 0.427937 0.999497 0.522298 0.999623 LAMP2 3920 A_23_P4

−1.41 0.054068 0.077326 0.759732 0.999497 0.672658 0.999623 SPON2 10417 A_23_P1

1.35 0.053374 0.077326 0.893937 0.999497 0.790237 0.999623 ING4 51147 A_23_P4

1.56 0.054062 0.077326 0.602712 0.999497 0.635273 0.999623 CXCL16 58191 A_23_P3

−1.2 0.053583 0.077326 0.945917 0.999497 0.989261 0.999623 AMICA1 120425 A_23_P1

−2.06 0.053736 0.077326 0.090903 0.999497 0.60496 0.999623 NPHP1 4867 A_24_P8

1.27 0.053724 0.077326 0.545708 0.999497 0.132466 0.999623 BUB1B 701 A_23_P1

1.48 0.053759 0.077326 0.811355 0.999497 0.876344 0.999623 SCARB1 949 A_23_P3

1.26 0.053636 0.077326 0.781537 0.999497 0.630622 0.999623 SMAD2 4087 A_24_P2

1.13 0.054062 0.077326 0.947205 0.999497 0.917569 0.999623 RAD52 5893 A_23_P6

1.28 0.053548 0.077326 0.876668 0.999497 0.263014 0.999623 CD151 977 A_23_P9

1.48 0.053984 0.077326 0.942078 0.999497 0.176278 0.999623 DERL1 79139 A_24_P1

−1.59 0.054229 0.077428 0.925115 0.999497 0.380825 0.999623 AEN 64782 A_32_P8

1.39 0.054207 0.077428 0.185031 0.999497 0.447625 0.999623 ZNF675 171392 A_23_P3

−3.09 0.054631 0.077937 0.755138 0.999497 0.526513 0.999623 EZR 7430 A_32_P1

−1.96 0.054723 0.078004 0.542415 0.999497 0.088239 0.999623 EDN2 1907 A_23_P3

1.38 0.054794 0.07804 0.31998 0.999497 0.750237 0.999623 TRAF5 7188 A_23_P2

1.2 0.054863 0.078075 0.198244 0.999497 0.688574 0.999623 CYCS 54205 A_24_P3

−1.96 0.054981 0.078125 0.303888 0.999497 0.309641 0.999623 SIGIRR 59307 A_23_P8

1.36 0.054989 0.078125 0.905737 0.999497 0.71141 0.999623 PICALM 8301 A_23_P1

−1.64 0.055061 0.078162 0.981661 0.999497 0.451614 0.999623 C8G 733 A_23_P2

1.72 0.055299 0.078435 0.800602 0.999497 0.265125 0.999623 CDH3 1001 A_23_P4

1.26 0.055548 0.078724 0.612362 0.999497 0.787921 0.999623 DNAJB6 10049 A_23_P2

−2.4 0.055707 0.078884 0.803694 0.999497 0.195436 0.999623 MAPT 4137 A_23_P2

1.28 0.05579 0.078937 0.668231 0.999497 0.577542 0.999623 NBN 4683 A_24_P2

−1.86 0.055899 0.079026 0.690918 0.999497 0.308075 0.999623 CLDN10 9071 A_23_P4

1.24 0.05598 0.079044 0.763734 0.999497 0.247918 0.999623 PSMC6 5706 A_23_P1

−1.59 0.056003 0.079044 0.58957 0.999497 0.683695 0.999623 C1D 10438 A_23_P6

−1.7 0.05632 0.079426 0.541511 0.999497 0.552801 0.999623 PKP4 8502 A_23_P1

−1.81 0.056369 0.07943 0.953047 0.999497 0.552642 0.999623 CREB1 1385 A_23_P7

−1.47 0.056448 0.079477 0.64991 0.999497 0.370657 0.999623 SAP30BP 29115 A_24_P3

1.43 0.056551 0.079556 0.611487 0.999497 0.593313 0.999623 KCNIP3 30818 A_23_P3

−1.38 0.056702 0.079703 0.982035 0.999497 0.844064 0.999623 FCGBP 8857 A_23_P2

1.64 0.056862 0.079864 0.636412 0.999497 0.219441 0.999623 RNF144B 255488 A_24_P4

−1.78 0.056909 0.079864 0.865156 0.999497 0.541439 0.999623 SIX4 51804 A_32_P2

−1.99 0.057173 0.080039 0.561118 0.999497 0.36626 0.999623 PACSIN1 29993 A_23_P2

1.39 0.057154 0.080039 0.242498 0.999497 0.709506 0.999623 MYEF2 50804 A_23_P7

−1.26 0.057136 0.080039 0.978938 0.999497 0.870922 0.999623 RAB4A 5867 A_23_P3

−1.43 0.057222 0.080043 0.989662 0.999497 0.391131 0.999623 FKBP15 23307 A_32_P2

1.33 0.057299 0.080086 0.687 0.999497 0.103788 0.999623 MUC4 4585 A_24_P2

−2.6 0.057632 0.080486 0.383032 0.999497 0.243007 0.999623 PAK2 5062 A_32_P1

1.59 0.057814 0.080675 0.584236 0.999497 0.717854 0.999623 NXT2 55916 A_24_P9

−1.64 0.058072 0.080969 0.881595 0.999497 0.390267 0.999623 STON2 85439 A_23_P3

1.7 0.058194 0.081008 0.436436 0.999497 0.02588 0.999623 LENG8 114823 A_24_P4

−1.3 0.05815 0.081008 0.933947 0.999497 0.932755 0.999623 PHLDA2 7262 A_23_P4

−1.69 0.058265 0.081042 0.397296 0.999497 0.248374 0.999623 NR3C1 2908 A_23_P2

1.3 0.058418 0.081189 0.093748 0.999497 0.896398 0.999623 RYR2 6262 A_23_P1

1.16 0.058594 0.08136 0.398575 0.999497 0.137126 0.999623 LOC442421 442421 A_23_P4

1.34 0.058636 0.08136 0.716192 0.999497 0.103469 0.999623 CASP2 835 A_24_P2

1.3 0.058887 0.081643 0.97231 0.999497 0.839865 0.999623 GAPVD1 26130 A_23_P3

−2.47 0.059076 0.08184 0.592779 0.999497 0.281485 0.999623 NP 4860 A_23_P1

1.38 0.059154 0.081881 0.590482 0.999497 0.952225 0.999623 TPT1 7178 A_24_P1

−1.49 0.059233 0.081905 0.643797 0.999497 0.754788 0.999623 PSMD1 5707 A_23_P2

−1.2 0.059266 0.081905 0.064632 0.999497 0.952043 0.999623 IGF1 3479 A_24_P3

1.5 0.059535 0.082145 0.508421 0.999497 0.954962 0.999623 GPR56 9289 A_23_P2

1.55 0.059494 0.082145 0.734577 0.999497 0.65396 0.999623 TLR6 10333 A_23_P2

1.41 0.059765 0.082396 0.723133 0.999497 0.717354 0.999623 BUB3 9184 A_23_P3

−2.01 0.059886 0.082497 0.385659 0.999497 0.55939 0.999623 UBB 7314 A_23_P2

1.68 0.060013 0.0825 0.293768 0.999497 0.480511 0.999623 NID1 4811 A_23_P2

−1.34 0.060032 0.0825 0.181672 0.999497 0.654073 0.999623 SEMA6A 57556 A_23_P7

1.38 0.059936 0.0825 0.558867 0.999497 0.473839 0.999623 HIPK2 28996 A_23_P1

2.3 0.060245 0.08259 0.794381 0.999497 0.739402 0.999623 PPIL3 53938 A_23_P2

1.27 0.060286 0.08259 0.262102 0.999497 0.165681 0.999623 ROCK1 6093 A_24_P5

−1.71 0.060289 0.08259 0.782182 0.999497 0.481754 0.999623 VNN1 8876 A_23_P2

1.39 0.060223 0.08259 0.364005 0.999497 0.722212 0.999623 BMP7 655 A_24_P9

1.62 0.060355 0.082615 0.597849 0.999497 0.77366 0.999623 UNC13B 10497 A_23_P2

1.45 0.060475 0.082714 0.152818 0.999497 0.241637 0.999623 PATL1 219988 A_23_P3

1.32 0.060673 0.082878 0.476153 0.999497 0.53564 0.999623 NME6 10201 A_23_P3

1.5 0.060756 0.082878 0.927312 0.999497 0.468945 0.999623 HSP90B1 7184 A_24_P1

−1.94 0.060787 0.082878 0.81706 0.999497 0.188363 0.999623 B3GNT5 84002 A_23_P1

−1.28 0.060787 0.082878 0.996076 0.999497 0.565651 0.999623 PVRL1 5818 A_23_P7

1.28 0.060875 0.082932 0.832488 0.999497 0.755851 0.999623 SFRP1 6422 A_23_P1

1.45 0.060928 0.082938 0.3416 0.999497 0.678176 0.999623 IGDCC3 9543 A_23_P3

1.36 0.061027 0.082952 0.477997 0.999497 0.145097 0.999623 CTSZ 1522 A_23_P4

−1.29 0.061034 0.082952 0.319291 0.999497 0.295555 0.999623 THBS3 7059 A_23_P2

1.32 0.061087 0.082958 0.976554 0.999497 0.443927 0.999623 MYL10 93408 A_23_P3

1.35 0.061208 0.082992 0.534713 0.999497 0.329238 0.999623 ITGB8 3696 A_23_P1

1.23 0.061199 0.082992 0.478355 0.999497 0.376422 0.999623 PVR 5817 A_32_P7

−1.43 0.061456 0.083215 0.957821 0.999497 0.265836 0.999623 METTL1 4234 A_23_P4

1.47 0.06147 0.083215 0.3862 0.999497 0.508648 0.999623 HES1 3280 A_24_P9

−1.36 0.061548 0.083255 0.295761 0.999497 0.529289 0.999623 TBRG4 9238 A_23_P2

1.25 0.061633 0.083262 0.36624 0.999497 0.981103 0.999623 FLJ23834 222256 A_32_P1

1.3 0.061649 0.083262 0.313687 0.999497 0.887795 0.999623 DGCR6L 85359 A_23_P1

1.39 0.061797 0.083397 0.412568 0.999497 0.314466 0.999623 ICAM1 3383 A_23_P1

1.31 0.062045 0.083404 0.680372 0.999497 0.634968 0.999623 STAT2 6773 A_23_P7

1.28 0.062019 0.083404 0.976264 0.999497 0.907148 0.999623 SLC1A6 6511 A_24_P1

1.47 0.061969 0.083404 0.598053 0.999497 0.712889 0.999623 APOC3 345 A_23_P2

1.44 0.061899 0.083404 0.929606 0.999497 0.205063 0.999623 ERCC3 2071 A_23_P5

1.16 0.061899 0.083404 0.959732 0.999497 0.917013 0.999623 UNC13D 201294 A_24_P5

1.55 0.062123 0.083445 0.778546 0.999497 0.769676 0.999623 POMP 51371 A_23_P6

−1.39 0.062428 0.083789 0.441242 0.999497 0.372817 0.999623 COL14A1 7373 A_24_P2

−2.11 0.062566 0.083863 0.33844 0.999497 0.744663 0.999623 PSME3 10197 A_24_P3

−2.48 0.06258 0.083863 0.322004 0.999497 0.898924 0.999623 LAMC1 3915 A_23_P2

−1.23 0.063032 0.084271 0.409845 0.999497 0.326379 0.999623 IFI27 3429 A_24_P2

−2.16 0.062994 0.084271 0.774557 0.999497 0.043282 0.999623 VCP 7415 A_32_P1

1.27 0.063002 0.084271 0.63139 0.999497 0.160201 0.999623 HLA-E 3133 A_23_P3

1.61 0.063098 0.084294 0.998624 0.999497 0.63157 0.999623 PTPRH 5794 A_23_P1

1.69 0.06328 0.084386 0.984408 0.999497 0.956971 0.999623 ID2 3398 A_32_P6

−1.69 0.06346 0.084386 0.430629 0.999497 0.797506 0.999623 THBS1 7057 A_32_P1

−1.28 0.063461 0.084386 0.485432 0.999497 0.565239 0.999623 HFE 3077 A_23_P3

1.58 0.063337 0.084386 0.236346 0.999497 0.053636 0.999623 ALCAM 214 A_32_P7

1.48 0.063406 0.084386 0.964084 0.999497 0.207685 0.999623 RALA 5898 A_23_P1

−1.86 0.063278 0.084386 0.10191 0.999497 0.298542 0.999623 PPP1R13L 10848 A_23_P1

1.55 0.063529 0.084412 0.731581 0.999497 0.521979 0.999623 C1QTNF3 114899 A_23_P1

−1.4 0.063721 0.084601 0.451521 0.999497 0.858492 0.999623 ITGA1 3672 A_23_P2

−1.17 0.063888 0.084698 0.876454 0.999497 0.578364 0.999623 SEMA3A 10371 A_24_P1

−1.96 0.063916 0.084698 0.979359 0.999497 0.515413 0.999623 HMGB1 3146 A_23_P9

−1.55 0.063941 0.084698 0.658136 0.999497 0.792064 0.999623 TRIM35 23087 A_23_P5

1.3 0.064022 0.084703 0.303103 0.999497 0.421854 0.999623 MAPK13 5603 A_23_P1

1.47 0.064043 0.084703 0.420345 0.999497 0.464172 0.999623 CDKN1B 1027 A_24_P8

−1.86 0.064135 0.084759 0.907395 0.999497 0.135679 0.999623 CTSS 1520 A_24_P2

−3.58 0.064236 0.084829 0.803693 0.999497 0.585641 0.999623 BIN1 274 A_24_P1

1.66 0.0643 0.084847 0.573023 0.999497 0.6276 0.999623 TNFRSF18 8784 A_24_P4

1.96 0.064504 0.084921 0.420216 0.999497 0.762135 0.999623 RAPGEF3 10411 A_32_P3

−1.46 0.064454 0.084921 0.423967 0.999497 0.871848 0.999623 GPR135 64582 A_23_P2

1.14 0.064458 0.084921 0.336918 0.999497 0.45434 0.999623 RAD51 5888 A_23_P8

2.16 0.064646 0.085043 0.74582 0.999497 0.723942 0.999623 CLN3 1201 A_23_P8

1.65 0.064885 0.085293 0.377334 0.999497 0.726209 0.999623 CASP10 843 A_23_P2

1.27 0.06517 0.085602 0.274417 0.999497 0.294492 0.999623 VCL 7414 A_24_P4

−1.74 0.065316 0.085729 0.173592 0.999497 0.637623 0.999623 HLA-DMA 3108 A_24_P5

1.37 0.065525 0.085741 0.769045 0.999497 0.176254 0.999623 CDH9 1007 A_23_P9

1.22 0.065399 0.085741 0.401308 0.999497 0.74778 0.999623 ABCA7 10347 A_23_P3

1.5 0.065482 0.085741 0.349054 0.999497 0.300378 0.999623 CUL3 8452 A_24_P1

1.21 0.06552 0.085741 0.194174 0.999497 0.186183 0.999623 IRF2BP1 26145 A_23_P9

1.56 0.065592 0.085764 0.530011 0.999497 0.171747 0.999623 PVRL4 81607 A_23_P4

1.31 0.065907 0.085791 0.898216 0.999497 0.289891 0.999623 SEMA5A 9037 A_24_P9

−1.43 0.065961 0.085791 0.086627 0.999497 0.657199 0.999623 NFKBIZ 64332 A_23_P2

1.18 0.065715 0.085791 0.732808 0.999497 0.450879 0.999623 PML 5371 A_23_P3

1.49 0.065847 0.085791 0.232513 0.999497 0.950817 0.999623 LGALS1 3956 A_23_P1

1.2 0.065827 0.085791 0.452585 0.999497 0.43499 0.999623 XRCC3 7517 A_23_P4

1.42 0.065881 0.085791 0.812737 0.999497 0.280094 0.999623 VPS45 11311 A_24_P3

1.26 0.065935 0.085791 0.760386 0.999497 0.366523 0.999623 CD99 4267 A_23_P2

1.37 0.066036 0.085824 0.415802 0.999497 0.877285 0.999623 NFATC4 4776 A_23_P1

1.56 0.066216 0.085933 0.278112 0.999497 0.880446 0.999623 HIP1 3092 A_24_P5

−1.32 0.066219 0.085933 0.973124 0.999497 0.968862 0.999623 LAT 27040 A_23_P6

1.45 0.066315 0.085992 0.739856 0.999497 0.527527 0.999623 TDGF1 6997 A_23_P3

2.44 0.066785 0.086537 0.286719 0.999497 0.420839 0.999623 GDF11 10220 A_23_P7

1.63 0.067033 0.086792 0.614453 0.999497 0.67061 0.999623 IGFN1 91156 A_32_P4

1.4 0.067271 0.08697 0.467572 0.999497 0.627504 0.999623 COPG2 26958 A_23_P6

−1.54 0.067235 0.08697 0.842821 0.999497 0.770027 0.999623 CD74 972 A_23_P7

1.44 0.067389 0.087057 0.836028 0.999497 0.142043 0.999623 TLR3 7098 A_23_P2

−1.44 0.067634 0.087309 0.005284 0.999497 0.41004 0.999623 NFE2L2 4780 A_23_P5

−1.49 0.067864 0.087539 0.557611 0.999497 0.55885 0.999623 ERCC6 2074 A_23_P1

−1.16 0.068412 0.088181 0.167979 0.999497 0.103066 0.999623 XRCC6 2547 A_23_P1

1.55 0.068528 0.088196 0.876559 0.999497 0.595161 0.999623 FNBP1 23048 A_23_P3

1.22 0.068502 0.088196 0.210089 0.999497 0.109915 0.999623 RAB34 83871 A_23_P1

1.36 0.068578 0.088196 0.164692 0.999497 0.609719 0.999623 FCRLA 84824 A_23_P4

1.44 0.068685 0.088268 0.413456 0.999497 0.767929 0.999623 SELPLG 6404 A_23_P6

1.7 0.068895 0.088472 0.978322 0.999497 0.293404 0.999623 PCMT1 5110 A_24_P2

−1.66 0.069042 0.088595 0.982318 0.999497 0.32771 0.999623 IL1R1 3554 A_24_P2

1.34 0.06911 0.088616 0.32048 0.999497 0.293248 0.999623 ALG1 56052 A_24_P5

1.67 0.069308 0.088803 0.375108 0.999497 0.758572 0.999623 ROCK2 9475 A_23_P2

−1.68 0.069371 0.088819 0.807761 0.999497 0.569649 0.999623 MUC5B 727897 A_24_P3

−1.42 0.069701 0.088911 0.844397 0.999497 0.58056 0.999623 PTPN1 5770 A_23_P3

−1.46 0.069674 0.088911 0.697717 0.999497 0.372209 0.999623 PSMD3 5709 A_24_P2

1.85 0.069639 0.088911 0.721566 0.999497 0.556409 0.999623 CDH6 1004 A_23_P2

1.29 0.069576 0.088911 0.849494 0.999497 0.484046 0.999623 COL20A1 57642 A_32_P8

−1.58 0.069579 0.088911 0.318531 0.999497 0.288065 0.999623 HESX1 8820 A_23_P1

1.2 0.069763 0.088924 0.119815 0.999497 0.60995 0.999623 UBE4B 10277 A_23_P2

−1.38 0.070071 0.089251 0.911792 0.999497 0.876165 0.999623 PLAU 5328 A_23_P2

1.15 0.070349 0.089314 0.92319 0.999497 0.628993 0.999623 IFI16 3428 A_23_P2

1.43 0.070218 0.089314 0.50821 0.999497 0.640024 0.999623 MAEA 10296 A_23_P2

1.21 0.07038 0.089314 0.25731 0.999497 0.481224 0.999623 UBB 7314 A_24_P1

2.48 0.070303 0.089314 0.123697 0.999497 0.49861 0.999623 HEPACAM 220296 A_24_P2

1.21 0.070325 0.089314 0.234704 0.999497 0.189901 0.999623 CASP2 835 A_23_P3

−1.85 0.070579 0.089501 0.924106 0.999497 0.363611 0.999623 TTYH1 57348 A_23_P5

1.46 0.070699 0.089543 0.932101 0.999497 0.844342 0.999623 MAPK3 5595 A_23_P3

1.36 0.070716 0.089543 0.518378 0.999497 0.496882 0.999623 CYBB 1536 A_23_P2

1.25 0.070904 0.089706 0.557522 0.999497 0.935803 0.999623 AZGP1 563 A_23_P7

1.23 0.070949 0.089706 0.341404 0.999497 0.942304 0.999623 LRP1 4035 A_23_P1

1.42 0.071153 0.089898 0.32079 0.999497 0.58229 0.999623 NFE2 4778 A_23_P1

1.23 0.071239 0.089941 0.467874 0.999497 0.800485 0.999623 MAP3K10 4294 A_24_P2

1.73 0.071317 0.089973 0.797461 0.999497 0.915787 0.999623 TUBB 203068 A_32_P7

1.15 0.071646 0.090323 0.774126 0.999497 0.148739 0.999623 ITGA5 3678 A_23_P3

1.47 0.071722 0.090351 0.890551 0.999497 0.297712 0.999623 CTSE 1510 A_23_P1

−1.26 0.071836 0.09043 0.799191 0.999497 0.612963 0.999623 ELN 2006 A_24_P1

−1.8 0.071983 0.090482 0.959394 0.999497 0.495364 0.999623 CLU 1191 A_23_P2

1.21 0.071959 0.090482 0.6467 0.999497 0.281353 0.999623 MSX2 4488 A_24_P1

−2.12 0.072309 0.09076 0.356266 0.999497 0.638407 0.999623 FBLN5 10516 A_23_P1

1.26 0.072289 0.09076 0.421469 0.999497 0.434594 0.999623 PPT1 5538 A_24_P2

1.33 0.072512 0.090948 0.876872 0.999497 0.343297 0.999623 DOCK7 85440 A_24_P2

1.34 0.072634 0.091035 0.223385 0.999497 0.851233 0.999623 PARVG 64098 A_23_P2

1.35 0.072897 0.091298 0.769423 0.999497 0.641898 0.999623 DAXX 1616 A_23_P1

1.36 0.073115 0.091373 0.904887 0.999497 0.844909 0.999623 CD300A 11314 A_24_P1

−3.19 0.073035 0.091373 0.853224 0.999497 0.635397 0.999623 CD300C 10871 A_23_P2

1.25 0.073077 0.091373 0.29654 0.999497 0.432398 0.999623 HLA-DPB1 3115 A_24_P1

1.66 0.073373 0.091561 0.829101 0.999497 0.406965 0.999623 TERF1 7013 A_23_P2

−1.68 0.073368 0.091561 0.713932 0.999497 0.338605 0.999623 SPP1 6696 A_23_P7

−1.53 0.073483 0.091632 0.656317 0.999497 0.215219 0.999623 PCDHB16 57717 A_23_P3

−1.3 0.073663 0.091791 0.84965 0.999497 0.198622 0.999623 CD244 51744 A_24_P1

−1.58 0.073895 0.091947 0.755374 0.999497 0.621937 0.999623 SRPK2 6733 A_23_P4

−1.68 0.073858 0.091947 0.582662 0.999497 0.317296 0.999623 HLA-DRB4 3126 A_24_P3

1.89 0.074152 0.0922 0.792213 0.999497 0.240951 0.999623 CD37 951 A_24_P8

1.71 0.074286 0.092233 0.303824 0.999497 0.979279 0.999623 RHOA 387 A_24_P1

1.28 0.074234 0.092233 0.067586 0.999497 0.830572 0.999623 RB1 5925 A_24_P1

−1.28 0.07469 0.092602 0.616952 0.999497 0.739005 0.999623 SOCS5 9655 A_24_P3

−1.62 0.074675 0.092602 0.292014 0.999497 0.228861 0.999623 NEK6 10783 A_23_P2

1.6 0.07497 0.092679 0.694387 0.999497 0.565284 0.999623 PCDHB15 56121 A_23_P1

−1.26 0.074951 0.092679 0.759314 0.999497 0.36976 0.999623 TGFBR1 7046 A_32_P1

1.38 0.074864 0.092679 0.292577 0.999497 0.259074 0.999623 DAPL1 92196 A_23_P1

1.28 0.074982 0.092679 0.051096 0.999497 0.958694 0.999623 NR2E1 7101 A_23_P3

1.22 0.075021 0.092679 0.601793 0.999497 0.556365 0.999623 HSPA9 3313 A_24_P7

−1.83 0.075085 0.092691 0.63554 0.999497 0.555625 0.999623 PSMG1 8624 A_23_P6

1.35 0.075234 0.092809 0.130119 0.999497 0.099576 0.999623 CREBBP 1387 A_23_P1

1.63 0.076077 0.093586 0.75556 0.999497 0.596916 0.999623 RECQL4 9401 A_23_P7

1.31 0.076082 0.093586 0.751386 0.999497 0.876279 0.999623 IFIT5 24138 A_24_P3

−1.52 0.075929 0.093586 0.410888 0.999497 0.220902 0.999623 BUB3 9184 A_23_P2

−1.27 0.076012 0.093586 0.225825 0.999497 0.138415 0.999623 AP2A2 161 A_23_P2

1.11 0.07617 0.093629 0.524319 0.999497 0.916485 0.999623 SCARF1 8578 A_23_P1

1.32 0.076793 0.094193 0.751116 0.999497 0.821842 0.999623 SNAP25 6616 A_23_P2

1.25 0.076778 0.094193 0.840024 0.999497 0.388759 0.999623 NLRC3 197358 A_23_P3

−1.31 0.076715 0.094193 0.781645 0.999497 0.681294 0.999623 DSC2 1824 A_23_P4

−2.67 0.077134 0.094544 0.023971 0.999497 0.756781 0.999623 ALDH1A2 8854 A_24_P7

−2.72 0.077249 0.094617 0.102973 0.999497 0.417413 0.999623 BAD 572 A_23_P1

1.39 0.077703 0.095105 0.927524 0.999497 0.277576 0.999623 HSPG2 3339 A_23_P2

1.29 0.077788 0.095142 0.631973 0.999497 0.991037 0.999623 VEGFA 7422 A_24_P1

−2.86 0.077975 0.095168 0.693386 0.999497 0.176198 0.999623 NPC1 4864 A_23_P1

−1.17 0.077911 0.095168 0.376908 0.999497 0.620903 0.999623 GPR183 1880 A_23_P2

−1.22 0.077926 0.095168 0.510821 0.999497 0.71278 0.999623 SEMA3F 6405 A_24_P3

1.36 0.078435 0.095595 0.765867 0.999497 0.93079 0.999623 PDPN 10630 A_24_P2

1.39 0.078386 0.095595 0.704501 0.999497 0.153662 0.999623 TRPC4AP 26133 A_23_P1

1.49 0.078556 0.095642 0.722258 0.999497 0.544348 0.999623 BLNK 29760 A_24_P6

−1.53 0.078585 0.095642 0.340908 0.999497 0.521439 0.999623 ZAP70 7535 A_24_P1

1.4 0.078715 0.095732 0.987112 0.999497 0.741617 0.999623 HINT1 3094 A_32_P3

−1.52 0.078936 0.095866 0.823136 0.999497 0.201455 0.999623 HRH1 3269 A_24_P2

−1.39 0.078892 0.095866 0.870706 0.999497 0.123979 0.999623 NFKBID 84807 A_23_P3

2.26 0.079123 0.095958 0.503013 0.999497 0.563525 0.999623 VTN 7448 A_23_P7

1.44 0.079123 0.095958 0.620538 0.999497 0.513387 0.999623 PRKRIR 5612 A_24_P3

−1.71 0.079207 0.095992 0.689103 0.999497 0.204232 0.999623 CNTNAP3 79937 A_24_P4

1.29 0.079318 0.096058 0.686473 0.999497 0.535152 0.999623 ITGAE 3682 A_23_P2

−1.5 0.079398 0.096088 0.659209 0.999497 0.580435 0.999623 PTPRS 5802 A_24_P2

1.46 0.079634 0.096104 0.843672 0.999497 0.190119 0.999623 CCL23 6368 A_24_P3

1.3 0.079621 0.096104 0.459304 0.999497 0.68307 0.999623 NCF1 653361 A_32_P1

1.72 0.079532 0.096104 0.885633 0.999497 0.311725 0.999623 SRGN 5552 A_23_P8

−1.79 0.07953 0.096104 0.996046 0.999497 0.627648 0.999623 THYN1 29087 A_23_P2

−1.21 0.079778 0.09621 0.336967 0.999497 0.528377 0.999623 MBD4 8930 A_23_P9

−1.84 0.079838 0.096216 0.600026 0.999497 0.298133 0.999623 NAMPT 10135 A_23_P3

−1.66 0.080101 0.096465 0.339861 0.999497 0.921301 0.999623 IL10RA 3587 A_24_P1

−1.26 0.080304 0.096642 0.717485 0.999497 0.961952 0.999623 NFATC3 4775 A_24_P3

1.25 0.08054 0.096725 0.657845 0.999497 0.894317 0.999623 AIFM2 84883 A_23_P1

2.09 0.080542 0.096725 0.658303 0.999497 0.615127 0.999623 PARD3 56288 A_24_P3

1.33 0.080538 0.096725 0.37714 0.999497 0.802016 0.999623 RB1CC1 9821 A_23_P9

−1.4 0.080638 0.096774 0.329588 0.999497 0.782272 0.999623 SART1 9092 A_23_P8

1.42 0.08084 0.096917 0.850047 0.999497 0.844076 0.999623 SIK1 150094 A_23_P1

−1.54 0.08087 0.096917 0.757172 0.999497 0.29682 0.999623 SYNJ2BP 55333 A_23_P6

−1.51 0.081024 0.097034 0.952809 0.999497 0.552324 0.999623 ITGB3 3690 A_24_P3

1.52 0.081293 0.097289 0.672961 0.999497 0.574028 0.999623 NFKB2 4791 A_23_P2

1.48 0.081789 0.097353 0.713252 0.999497 0.415635 0.999623 ITGAM 3684 A_23_P1

−1.52 0.081799 0.097353 0.507717 0.999497 0.167789 0.999623 ACTN1 87 A_24_P1

1.34 0.081746 0.097353 0.585676 0.999497 0.911428 0.999623 MLL 4297 A_24_P2

1.21 0.081631 0.097353 0.031315 0.999497 0.930933 0.999623 ZYX 7791 A_23_P2

1.47 0.081758 0.097353 0.247784 0.999497 0.323588 0.999623 MAP4K3 8491 A_23_P1

1.38 0.081682 0.097353 0.840367 0.999497 0.770612 0.999623 CADPS2 93664 A_24_P2

1.34 0.081597 0.097353 0.271639 0.999497 0.373297 0.999623 SP110 3431 A_23_P1

1.18 0.081494 0.097353 0.874236 0.999497 0.958095 0.999623 PTPRC 5788 A_23_P1

−1.83 0.082063 0.097533 0.449752 0.999497 0.219033 0.999623 NRG1 3084 A_23_P1

1.38 0.082012 0.097533 0.820295 0.999497 0.783625 0.999623 APC 324 A_23_P7

1.34 0.082223 0.097622 0.503368 0.999497 0.99069 0.999623 PPID 5481 A_23_P3

−1.29 0.082251 0.097622 0.112933 0.999497 0.502935 0.999623 MUC16 94025 A_23_P5

1.26 0.082332 0.09765 0.996124 0.999497 0.893653 0.999623 PPP2CA 5515 A_23_P1

−1.74 0.082538 0.097761 0.9949 0.999497 0.337659 0.999623 SHISA5 51246 A_24_P3

1.15 0.082493 0.097761 0.853586 0.999497 0.199523 0.999623 CSNK1E 1454 A_23_P4

1.57 0.082721 0.09791 0.61832 0.999497 0.465145 0.999623 OLFML3 56944 A_24_P1

1.42 0.082811 0.097949 0.613862 0.999497 0.763098 0.999623 TAF1 6872 A_23_P1

1.14 0.082967 0.097999 0.651317 0.999497 0.540961 0.999623 TAPBP 6892 A_23_P3

1.31 0.082916 0.097999 0.718623 0.999497 0.192495 0.999623 FKBP14 55033 A_23_P2

1.25 0.083196 0.098026 0.216126 0.999497 0.602589 0.999623 SFRP1 6422 A_23_P1

−1.27 0.083274 0.098026 0.668156 0.999497 0.333082 0.999623 BIRC2 329 A_24_P1

−1.3 0.083139 0.098026 0.591219 0.999497 0.546934 0.999623 IRF2BP2 359948 A_23_P4

1.23 0.083234 0.098026 0.394959 0.999497 0.922887 0.999623 PBX1 5087 A_32_P2

−1.97 0.083121 0.098026 0.784926 0.999497 0.536081 0.999623 TNNI2 7136 A_23_P2

1.56 0.083615 0.098293 0.807774 0.999497 0.599572 0.999623 IL15RA 3601 A_23_P1

1.19 0.083599 0.098293 0.696413 0.999497 0.946544 0.999623 CDH10 1008 A_23_P1

1.21 0.083968 0.098305 0.420776 0.999497 0.601302 0.999623 CD244 51744 A_23_P8

−1.77 0.083696 0.098305 0.243443 0.999497 0.375803 0.999623 ITM2B 9445 A_24_P3

−1.86 0.083903 0.098305 0.770656 0.999497 0.339055 0.999623 IFI30 10437 A_23_P1

1.12 0.083774 0.098305 0.88359 0.999497 0.700128 0.999623 ICA1L 130026 A_23_P1

1.29 0.083937 0.098305 0.722955 0.999497 0.175536 0.999623 IGFBP3 3486 A_24_P3

1.3 0.083937 0.098305 0.46092 0.999497 0.220558 0.999623 FN1 2335 A_24_P3

1.31 0.084151 0.098452 0.412248 0.999497 0.587847 0.999623 TOP2A 7153 A_23_P1

−1.73 0.084298 0.098558 0.926046 0.999497 0.168959 0.999623 SON 6651 A_23_P4

1.11 0.084404 0.098614 0.932948 0.999497 0.632745 0.999623 CDSN 1041 A_23_P7

−1.61 0.084463 0.098617 0.76982 0.999497 0.191428 0.999623 FADD 8772 A_24_P2

1.45 0.084708 0.098835 0.609665 0.999497 0.486097 0.999623 CD69 969 A_23_P8

−1.78 0.084882 0.098972 0.821948 0.999497 0.312215 0.999623 PRKDC 5591 A_32_P2

1.21 0.085014 0.099059 0.45833 0.999497 0.569214 0.999623 SMO 6608 A_23_P7

1.29 0.085095 0.099087 0.831629 0.999497 0.524877 0.999623 SLC23A2 9962 A_24_P2

−1.65 0.08528 0.099179 0.899964 0.999497 0.233504 0.999623 RGN 9104 A_23_P1

−1.12 0.085348 0.099179 0.745361 0.999497 0.499128 0.999623 SORT1 6272 A_24_P3

−1.25 0.085323 0.099179 0.635433 0.999497 0.327292 0.999623 ABCC4 10257 A_24_P1

−1.21 0.085631 0.099441 0.191325 0.999497 0.36813 0.999623 IFI16 3428 A_23_P1

−2.13 0.085924 0.099647 0.995129 0.999497 0.586429 0.999623 CNTNAP3 79937 A_23_P9

1.4 0.085906 0.099647 0.988668 0.999497 0.86938 0.999623 SEMA3A 10371 A_23_P3

−1.44 0.085985 0.09965 0.802566 0.999497 0.807389 0.999623 PVRIG 79037 A_23_P8

1.3 0.086042 0.09965 0.843982 0.999497 0.296462 0.999623 CITED2 10370 A_32_P1

1.25 0.086437 0.09991 0.741042 0.999497 0.879654 0.999623 AIFM3 150209 A_23_P2

1.35 0.08644 0.09991 0.488209 0.999497 0.771895 0.999623 IFNAR2 3455 A_23_P2

1.32 0.086353 0.09991 0.773614 0.999497 0.613828 0.999623 PTGES3 10728 A_24_P3

1.18 0.086501 0.099913 0.592575 0.999497 0.694156 0.999623 RPS3A 6189 A_32_P2

−1.93 0.086597 0.099957 0.354189 0.999497 0.642821 0.999623 FGG 2266 A_23_P1

−2.2 0.086676 0.099981 0.21771 0.999497 0.480389 0.999623 0 0 0 1 0 0 0 0 1 0 0 0 1 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 1 0 1 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 1 1 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 1 0 0 0 0 2 0 0 0 0 0 0 0 0 0 2 1 2 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 1 0 0 0 0 0 0 0 0 1 0 1 0 2 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 2 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 2 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 1 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 1 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 1 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 1 1 0 0 1 1 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 1 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 2 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 1 0 0 0 0 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 1 0 0 0 0 1 0 0 0 1 0 1 0 0 1 0 0 0 1 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 1 1 0 1 0 0 0 0 0 0 0 0 1 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 1 2 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 1 0 2 1 0 0 0 0 0 0 0 0 0 0 0 0

indicates data missing or illegible when filed

APPENDIX H

TABLE S8 Medication category listing for CR and CNR Medication/Medication Number of CR taking Number of CNR Medical Code Category Name combination taken medication taking medication  1 Analgesics/NSAIDS Advil 1  1 Analgesics/NSAIDS Naproxen 1  3 Antacids/H2 antagonists: Zantac 1  5 Anti-asthma/bronchodilators Flovent 1  5 Anti-asthma/bronchodilators Beclate-100, Tiotropium 1 Bromide  6 Anti-cholesterol/Anti- Mevacor, Zocor 1 hyperlipidemic  6 Anti-cholesterol/Anti- Liptor 1 hyperlipidemic  7 Anti-coagulants Coumadin 1  7 Anti-coagulants Aggrenox 1  7 Anti-coagulants Warfarin 1  7 Anti-coagulants Aspirin 3  8 Antibiotics/anti-infectives/anti- Augmentin 1 parasitics/anti-microbials  9 Antidepressants/mood-altering Prozac 1 drugs 10 Antihistamines/Decongestants Loratadine 1 10 Antihistamines/Decongestants NyQuil 1 11, 12 Antihypertensives and Maxzide 1 Cardiovascular, other than hyperlipidemic/HTN 11, 12 Antihypertensives and Lisinopril, 1 Cardiovascular, other than Hydrochorothiazide hyperlipidemic/HTN 11, 12 Antihypertensives and Lisinopril, Metoprolol 1 Cardiovascular, other than hyperlipidemic/HTN 11, 12 Antihypertensives and Lisinopril; Lasix; Atenol 1 Cardiovascular, other than hyperlipidemic/HTN 11, 12 Antihypertensives and Atenol; Captopril; 1 Cardiovascular, other than Furosemide hyperlipidemic/HTN 11, 12 Antihypertensives and Diltiazem 1 Cardiovascular, other than hyperlipidemic/HTN 15 Endocrine/Metabolic agents Fosamax 1 15 Endocrine/Metabolic agents Levothroid 1 1 18 Hormones/steroids Estradiol 1 18 Hormones/steroids Premarin 1 21 Vitamins, minerals, food Vitamin D; Aplpha- 1 supplements Lipoic Acid; Multi- vitamin, Tumeric Acid 21 Vitamins, minerals, food Calcium with Vitamin D 1 supplements 21 Vitamins, minerals, food Ferrous Sulphate 1 supplements 21 Vitamins, minerals, food Multi-vitamin 2 supplements 99 Other Allopurinol 1 99 Other Doxazosin 1 99 Other Terazosin 1 99 Other Potassium Cholride 1

APPENDIX I

TABLE S9 Age associated differences common to both CR and CNR Name FC CR vs Yng FC CNR vs Yng QV CR vs Yng QC CNR vs Yng phenoD GAMMA DELTA −3.5 −1.4 0.12 0.2 CELLS phenoD MONOCYTES 1.3 1.1 0.16 0.17 CytM EOTAXIN 2 1.4 0.02 0.17 cytM IP10 1.8 1.8 0.05 0.15 pfD cd8_IFNa_STAT1 −1.4 −4 0.11 0 pfD cd8_IL21_STAT1 −1.4 −2.1 0.11 0 pfBaselineD cd8_Unstimulated_STAT5 1.1 1.1 0.09 0.02 pfBaselineD cd8_Unstimulated_STAT3 1.2 1.2 0.09 0 pfBaselineD cd8_Unstimulated_STAT1 1.6 1.7 0.05 0 geD NUDCD2 −2.1 −1.9 0.02 0.07 geD CTNND2 −2 −1.9 0.02 0.13 geD TNFRSF11A −1.3 −1.8 0.05 0.07 geD HIVEP3 −1.2 −1.7 0.12 0.07 geD NF2 −1.7 −1.7 0.02 0.17 geD BAG5 −1.4 −1.6 0.03 0.07 geD IGF2BP2 −1.4 −1.6 0.04 0.07 geD CDH1 −1.8 −1.6 0.02 0.1 geD CEACAM6 −1.3 −1.6 0.06 0.11 geD PSME1 −1.6 −1.6 0.05 0.12 geD TNFAIP8L1 −1.5 −1.6 0.04 0.13 geD CARD14 −1.3 −1.6 0.06 0.13 geD SMAD3 −1.3 −1.6 0.11 0.17 geD FRK −1.5 −1.5 0.02 0.07 geD NLGN4X −1.4 −1.5 0.02 0.07 geD NF2 −1.3 −1.5 0.05 0.07 geD SARNP −1.3 −1.5 0.05 0.07 geD XRCC6 −1.2 −1.5 0.03 0.07 geD FLJ23834 −1.1 −1.5 0.12 0.07 geD CTNNAL1 −2 −1.5 0.04 0.1 geD ERC1 −1.3 −1.5 0.06 0.1 geD ICA1L −1.2 −1.5 0.12 0.1 geD PCDH7 −1.2 −1.5 0.15 0.1 geD PEA15 −1.4 −1.5 0.12 0.11 geD RIMS2 −1.3 −1.5 0.06 0.11 geD ROBO1 −1.3 −1.5 0.06 0.11 geD CDH13 −1.7 −1.5 0.02 0.12 geD RABEP1 −3.3 −1.5 0.02 0.14 geD REL −1.4 −1.5 0.04 0.14 geD C14orf153 −1.4 −1.5 0.11 0.14 geD FGA −1.2 −1.5 0.09 0.14 geD IFT52 −1.5 −1.5 0.06 0.15 geD LEAP2 −1.4 −1.5 0.06 0.15 geD FCRLA −1.3 −1.5 0.09 0.15 geD HM13 −1.2 −1.5 0.18 0.15 geD MAGI1 −1.3 −1.5 0.04 0.17 geD NDUFS1 −1.2 −1.5 0.12 0.17 geD SOCS4 −1.6 −1.5 0.05 0.18 geD RAC1 −1.8 −1.5 0.02 0.19 geD SIK2 −1.3 −1.5 0.09 0.19 geD AP1G1 −2 −1.4 0.02 0.07 geD ATP5B −1.9 −1.4 0.03 0.07 geD STXBP5 −1.6 −1.4 0.03 0.07 geD APEX1 −1.6 −1.4 0.07 0.07 geD DLL3 −1.5 −1.4 0.09 0.07 geD PUF60 −1.4 −1.4 0.08 0.07 geD SEMA5A −1.3 −1.4 0.03 0.07 geD BCAP29 −1.3 −1.4 0.04 0.07 geD INCENP −1.3 −1.4 0.05 0.07 geD EXOC6 −1.3 −1.4 0.05 0.07 geD IL17D −1.3 −1.4 0.07 0.07 geD PTPN11 −1.2 −1.4 0.06 0.07 geD PPARA −1.2 −1.4 0.07 0.07 geD DLC1 −1.2 −1.4 0.12 0.07 geD MIB1 −1.1 −1.4 0.15 0.07 geD ITGB8 −1.1 −1.4 0.16 0.07 geD MAP4K4 −2.5 −1.4 0.02 0.08 geD THRA −1.8 −1.4 0.03 0.08 geD CD1E −1.6 −1.4 0.18 0.09 geD RFFL −1.3 −1.4 0.12 0.09 geD CLN8 −1.2 −1.4 0.12 0.09 geD SOCS5 −1.2 −1.4 0.15 0.09 geD CDH4 −1.1 −1.4 0.18 0.09 geD EBF1 −1.3 −1.4 0.03 0.1 geD XCL2 −1.3 −1.4 0.04 0.1 geD DNM3 −1.3 −1.4 0.04 0.1 geD FXR1 −1.3 −1.4 0.06 0.1 geD PTGER2 −1.5 −1.4 0.02 0.11 geD SMAD1 −1.3 −1.4 0.03 0.11 geD SLTM −1.8 −1.4 0.04 0.12 geD SNAP29 −1.5 −1.4 0.03 0.12 geD TLN2 −1.5 −1.4 0.07 0.12 geD PPFIBP1 −1.4 −1.4 0.02 0.12 geD IL28RA −1.3 −1.4 0.04 0.12 geD EFNB1 −1.1 −1.4 0.18 0.12 geD STEAP2 −2 −1.4 0.02 0.13 geD USP33 −1.5 −1.4 0.02 0.13 geD IRAK4 −1.5 −1.4 0.05 0.13 geD TGFB2 −1.4 −1.4 0.03 0.13 geD PRUNE2 −1.4 −1.4 0.06 0.13 geD CASP9 −1.3 −1.4 0.06 0.13 geD PSMB1 −1.2 −1.4 0.12 0.13 geD PHB −1.2 −1.4 0.14 0.13 geD TIA1 −1.3 −1.4 0.07 0.14 geD SP3 −1.2 −1.4 0.18 0.14 geD ASB1 −1.1 −1.4 0.17 0.14 geD MIA3 −1.6 −1.4 0.02 0.15 geD PCDH9 −1.3 −1.4 0.07 0.15 geD NOD2 −1.3 −1.4 0.09 0.15 geD NEK11 −1.3 −1.4 0.1 0.15 geD ERMAP −1.2 −1.4 0.08 0.15 geD DYRK2 −1.6 −1.4 0.02 0.16 geD HMGB2 −1.5 −1.4 0.03 0.16 geD RSPH1 −1.4 −1.4 0.05 0.16 geD RALBP1 −1.4 −1.4 0.11 0.16 geD FKBP1B −1.3 −1.4 0.1 0.16 geD ZFYVE9 −1.2 −1.4 0.13 0.16 geD IL13RA1 −1.2 −1.4 0.13 0.16 geD SOD2 −1.6 −1.4 0.02 0.17 geD ERAP1 −1.2 −1.4 0.17 0.17 geD APAF1 −2.8 −1.4 0.02 0.18 geD ELMOD2 −1.4 −1.4 0.05 0.18 geD COL3A1 −1.5 −1.4 0.09 0.19 geD MCAM −1.4 −1.4 0.12 0.19 geD PSMB1 −1.3 −1.4 0.07 0.19 geD TCTN3 −1.9 −1.3 0.07 0.07 geD PTGR1 −1.8 −1.3 0.02 0.07 geD IL7 −1.4 −1.3 0.04 0.07 geD TPBG −1.4 −1.3 0.05 0.07 geD DDR2 −1.3 −1.3 0.12 0.07 geD C7orf16 −1.2 −1.3 0.05 0.07 geD MYST4 −1.1 −1.3 0.18 0.07 geD TSLP −1.1 −1.3 0.2 0.07 geD L3MBTL4 −1.5 −1.3 0.03 0.09 geD CMTM8 −1.4 −1.3 0.02 0.09 geD PTGR2 −1.2 −1.3 0.02 0.09 geD CDC42 −1.5 −1.3 0.03 0.1 geD MASP1 −1.4 −1.3 0.02 0.1 geD DMBT1 −1.2 −1.3 0.02 0.1 geD TAOK2 −1.6 −1.3 0.04 0.11 geD DNM1L −1.4 −1.3 0.03 0.11 geD FXR1 −1.2 −1.3 0.11 0.11 geD B3GALNT1 −1.1 −1.3 0.2 0.11 geD PSMA4 −1.6 −1.3 0.02 0.12 geD RRAGA −1.5 −1.3 0.03 0.12 geD IGBP1 −1.4 −1.3 0.02 0.12 geD ABL1 −1.2 −1.3 0.05 0.12 geD CRADD −1.2 −1.3 0.09 0.12 geD C9orf61 −1.1 −1.3 0.1 0.12 geD PURB −1.5 −1.3 0.02 0.13 geD DSTN −1.4 −1.3 0.03 0.13 geD CXCL12 −1.3 −1.3 0.04 0.13 geD PLDN −1.6 −1.3 0.03 0.14 geD SULF1 −1.5 −1.3 0.03 0.14 geD FKBP10 −1.4 −1.3 0.04 0.14 geD BUB3 −1.3 −1.3 0.06 0.14 geD BMP2 −1.3 −1.3 0.07 0.14 geD MIG7 −1.2 −1.3 0.09 0.14 geD CMTM4 −1.2 −1.3 0.19 0.14 geD SEMA5A −1.9 −1.3 0.02 0.15 geD DCBLD1 −1.5 −1.3 0.03 0.15 geD DRAM −1.4 −1.3 0.04 0.15 geD SIK1 −1.3 −1.3 0.1 0.15 geD PLG −1.5 −1.3 0.02 0.16 geD HNMT −1.4 −1.3 0.03 0.16 geD TNFRSF19 −1.3 −1.3 0.05 0.16 geD IFT140 −1.1 −1.3 0.09 0.16 geD CUL1 −1.1 −1.3 0.16 0.16 geD IL1RAP −1.6 −1.3 0.03 0.17 geD CYCS −1.5 −1.3 0.02 0.17 geD PPM1F −1.3 −1.3 0.06 0.17 geD RNMTL1 −1.1 −1.3 0.17 0.17 geD RYR2 −1.1 −1.3 0.19 0.17 geD SMURF2 −1.8 −1.3 0.04 0.18 geD NF2 −1.7 −1.3 0.02 0.18 geD ZNF346 −1.5 −1.3 0.18 0.18 geD KRT18 −1.4 −1.3 0.02 0.18 geD CDC42SE2 −1.4 −1.3 0.04 0.18 geD RND1 −1.4 −1.3 0.08 0.18 geD NOTCH2 −1.4 −1.3 0.09 0.18 geD STK38 −1.4 −1.3 0.16 0.18 geD SMAD2 −1.3 −1.3 0.04 0.18 geD FNBP1L −1.3 −1.3 0.07 0.18 geD SNIP −1.3 −1.3 0.1 0.18 geD TRIB1 −1.2 −1.3 0.14 0.18 geD PPIC −1.5 −1.3 0.04 0.19 geD TGFBI −1.4 −1.3 0.06 0.19 geD TXLNA −1.3 −1.3 0.05 0.19 geD SLFN5 −1.3 −1.3 0.08 0.19 geD SMAD5 −1.2 −1.3 0.14 0.19 geD SON −1.6 −1.3 0.02 0.2 geD SWAP70 −1.5 −1.3 0.04 0.2 geD ALK −1.4 −1.3 0.06 0.2 geD AGGF1 −1.3 −1.3 0.11 0.2 geD CASP10 −1.5 −1.2 0.09 0.07 geD DIAPH2 −1.1 −1.2 0.19 0.1 geD GREM2 −1.3 −1.2 0.04 0.11 geD SPN −1.3 −1.2 0.1 0.12 geD HBXIP −1.2 −1.2 0.18 0.15 geD C14orf153 −1.7 −1.2 0.1 0.16 geD JAKMIP1 −1.3 −1.2 0.05 0.16 geD COL27A1 −1.3 −1.2 0.06 0.16 geD TIAM2 −1.1 −1.2 0.14 0.16 geD IK −1.2 −1.2 0.07 0.17 geD CD9 −1.1 −1.2 0.18 0.17 geD VNN1 −1.5 −1.2 0.03 0.18 geD IFT88 −1.5 −1.2 0.04 0.18 geD PTK2 −1.4 −1.2 0.06 0.18 geD SRA1 −1.2 −1.2 0.11 0.18 geD SNX1 −1.2 −1.2 0.12 0.18 geD PRKDC −1.3 −1.2 0.06 0.19 geD POLA1 −1.1 −1.2 0.19 0.19 geD FGG −2.6 −1.2 0.04 0.2 geD SNX4 −1.4 −1.2 0.1 0.2 geD FAT3 −1.2 −1.2 0.06 0.2 geD LOC645166 1.4 1.1 0.02 0.18 geD TUBB 1.4 1.2 0.02 0.1 geD FAF1 1.4 1.2 0.02 0.12 geD PSMB2 1.2 1.2 0.05 0.13 geD TH1L 1.3 1.2 0.02 0.14 geD MAEA 1.1 1.2 0.16 0.15 geD PVRL2 1.2 1.2 0.11 0.16 geD MPZL2 1.3 1.2 0.03 0.17 geD FKBP4 1.3 1.2 0.04 0.17 geD RBP4 1.3 1.2 0.02 0.18 geD LAMC2 1.6 1.2 0.02 0.2 geD CTSC 1.3 1.3 0.03 0.07 geD CASP4 1.3 1.3 0.04 0.07 geD BECN1 1.3 1.3 0.06 0.07 geD C2 1.7 1.3 0.02 0.1 geD EXOC7 1.4 1.3 0.03 0.12 geD CEACAM1 1.2 1.3 0.07 0.13 geD CCM2 1.4 1.3 0.13 0.14 geD PURB 1.3 1.3 0.05 0.15 geD CTSS 1.3 1.3 0.07 0.15 geD LGALS3BP 1.5 1.3 0.02 0.15 geD GPR135 1.2 1.3 0.12 0.16 geD MYLPF 1.3 1.3 0.09 0.16 geD MUC5AC 1.3 1.3 0.17 0.16 geD RHOA 1.7 1.3 0.02 0.17 geD GP6 1.5 1.3 0.03 0.19 geD IFI30 1.5 1.3 0.03 0.19 geD TNFAIP8 1.7 1.3 0.03 0.2 geD LITAF 1.2 1.4 0.1 0.07 geD EHD1 1.7 1.4 0.02 0.07 geD CNTNAP2 1.2 1.4 0.06 0.08 geD NRP1 1.3 1.4 0.04 0.11 geD WNK1 1.4 1.4 0.04 0.11 geD TNFAIP2 1.5 1.4 0.04 0.12 geD IFITM2 1.7 1.4 0.02 0.12 geD MLLT6 1.8 1.4 0.02 0.12 geD FCGR2A 1.3 1.4 0.03 0.14 geD SORL1 1.7 1.4 0.03 0.15 geD B3GALNT1 1.6 1.4 0.02 0.16 geD IGF2AS 1.6 1.4 0.03 0.16 geD CEBPB 2 1.4 0.02 0.16 geD CNTN2 1.3 1.4 0.03 0.17 geD LRRN2 1.8 1.4 0.02 0.17 geD THBS1 1.7 1.4 0.03 0.18 geD SLC13A2 1.2 1.4 0.17 0.19 geD ADRB3 1.2 1.5 0.15 0.07 geD CTF1 1.3 1.5 0.07 0.07 geD IRS2 1.4 1.5 0.02 0.07 geD SP3 1.2 1.5 0.13 0.08 geD LTBP2 1.4 1.5 0.04 0.1 geD ITFG3 1.2 1.5 0.14 0.12 geD STX1A 1.5 1.5 0.03 0.12 geD PRKCD 2.1 1.5 0.02 0.14 geD THRA 1.1 1.5 0.19 0.16 geD TAL1 1.4 1.5 0.07 0.16 geD PLEKHF1 2 1.5 0.02 0.16 geD CR2 1.3 1.5 0.12 0.18 geD ACTC1 1.4 1.5 0.09 0.18 geD NINJ2 1.7 1.5 0.03 0.18 geD LIMS2 2.1 1.5 0.03 0.18 geD LAMA4 1.2 1.5 0.17 0.19 geD GYLTL1B 1.8 1.5 0.04 0.19 geD RABEP1 2 1.5 0.04 0.19 geD G6PD 1.2 1.6 0.12 0.09 geD TNR 1.6 1.6 0.14 0.1 geD MASP2 1.4 1.6 0.06 0.11 geD PGM5 1.5 1.6 0.05 0.11 geD RAC2 2.2 1.6 0.02 0.12 geD ZFR2 1.7 1.6 0.04 0.13 geD UMOD 1.8 1.6 0.02 0.13 geD TNXB 1.4 1.6 0.09 0.14 geD EBI3 1.4 1.6 0.09 0.15 geD COL27A1 2 1.6 0.02 0.16 geD CEBPE 1.7 1.6 0.04 0.17 geD MMP9 1.9 1.6 0.03 0.19 geD CFD 2.2 1.6 0.03 0.19 geD DGKZ 2.1 1.6 0.03 0.2 geD APOA4 1.2 1.7 0.07 0.07 geD HLA-DPB1 1.4 1.7 0.08 0.07 geD IL28A 1.3 1.7 0.05 0.13 geD LILRA5 2 1.7 0.03 0.13 geD APOL2 1.9 1.7 0.03 0.14 geD GZMM 1.9 1.7 0.04 0.16 geD MYADM 1.7 1.7 0.05 0.17 geD SEMA4A 1.8 1.7 0.05 0.19 geD LY86 2.1 1.7 0.03 0.19 geD TNFSF13B 1.7 1.8 0.02 0.08 geD MAP4K2 1.3 1.8 0.09 0.1 geD IL12RB1 1.2 1.8 0.18 0.13 geD SSTR3 1.6 1.8 0.06 0.14 geD FOXH1 1.8 1.8 0.03 0.16 geD ZBP1 2.2 1.8 0.03 0.17 geD DEFB4 1.2 1.9 0.1 0.07 geD CASP5 1.6 1.9 0.07 0.08 geD RAPGEF3 1.3 1.9 0.18 0.1 geD PTGIR 1.6 1.9 0.07 0.1 geD HRH2 1.4 1.9 0.07 0.14 geD LSP1 2.3 1.9 0.03 0.14 geD ADAM33 2 1.9 0.06 0.15 geD WAS 2.1 1.9 0.03 0.16 geD CD244 1.3 2 0.09 0.07 geD CLDN11 1.6 2 0.04 0.07 geD MYADM 1.7 2 0.02 0.07 geD COL20A1 1.2 2 0.15 0.1 geD PEAR1 1.4 2 0.07 0.1 geD MUC2 1.3 2 0.11 0.12 geD LAT2 2.1 2 0.03 0.12 geD PSTPIP1 2.8 2.1 0.02 0.11 geD MARCO 2.1 2.1 0.07 0.16 geD UNC5A 1.1 2.1 0.2 0.19 geD FCN2 2 2.1 0.1 0.19 geD HLA-DPB1 3.6 2.1 0.02 0.19 geD CD300LB 1.9 2.2 0.02 0.07 geD HLA-F 2.2 2.2 0.02 0.07 geD LILRA5 3.2 2.2 0.02 0.07 geD CASP8 1.7 2.2 0.09 0.1 geD GHRHR 1.9 2.2 0.05 0.1 geD PIK3CD 2.5 2.2 0.02 0.13 geD ITGB2 1.8 2.2 0.05 0.16 geD IRF1 2.8 2.2 0.04 0.2 geD FCGBP 1.3 2.3 0.2 0.1 geD TREML1 1.7 2.3 0.06 0.1 geD PDGFRB 1.7 2.3 0.1 0.17 geD ERCC2 2.2 2.4 0.02 0.07 geD SLC5A2 2.2 2.4 0.04 0.14 geD IL10RA 1.9 2.4 0.1 0.16 geD MUC4 1.8 2.4 0.12 0.18 geD NKX2-3 1.6 2.5 0.08 0.07 geD HRH3 2.4 2.5 0.08 0.1 geD CDSN 1.6 2.6 0.06 0.07 geD MINK1 2 2.6 0.04 0.1 geD ACVR1B 2 2.7 0.03 0.07 geD UCP3 2.8 2.7 0.02 0.07 geD MUC4 1.9 2.7 0.06 0.1 geD PTCRA 1.6 2.7 0.14 0.12 geD PROP1 1.7 2.7 0.12 0.12 geD HLA-J 3.9 2.7 0.02 0.16 geD POLM 2.1 2.7 0.1 0.18 geD KIR2DL4 1.7 2.8 0.06 0.07 geD GYPC 2.1 2.8 0.03 0.07 geD CACNB3 2.4 2.8 0.07 0.15 geD LILRA3 2.8 2.8 0.06 0.16 geD LAX1 1.5 2.9 0.13 0.07 geD GHSR 1.6 2.9 0.1 0.07 geD RARA 1.7 2.9 0.12 0.1 geD RUNX1 2.2 3 0.04 0.07 geD HLA-B 3.4 3 0.04 0.1 geD HLA-DOA 3.5 3 0.03 0.14 geD JAK3 2.2 3.1 0.02 0.07 geD CEACAM19 2.8 3.1 0.04 0.15 geD CPLX2 2.6 3.3 0.06 0.12 geD TCL6 1.8 3.5 0.19 0.15 geD E2F2 2.1 3.6 0.03 0.14 geD PTAFR 5.6 3.7 0.03 0.18 geD HLA-DRB1 2.5 3.8 0.11 0.15 geD CD14 4.2 4 0.03 0.11 geD MUC4 1.6 4.1 0.06 0.07 geD LALBA 2.1 4.2 0.03 0.13 geD FCER1G 2.4 4.3 0.14 0.16 geD TAOK2 2.7 4.4 0.04 0.07 geD BCAM 2.9 4.4 0.07 0.13 geD MLXIPL 3.1 4.5 0.07 0.13 geD CCL24 2.6 4.6 0.1 0.14 geD HLA-DRB3 2.6 4.8 0.14 0.14 geD LILRA6 8.8 4.8 0.03 0.18 geD IL8RA 4.3 5 0.1 0.2 geD CD79A 4 5.7 0.08 0.15 geD HLA-DRB5 4.2 5.7 0.09 0.16 geD FCN1 4.6 5.7 0.09 0.18 geD BCL2 3.5 6 0.06 0.1 geD ADAMTS7 3.8 6.9 0.1 0.16 geD CD4 3.1 8.5 0.07 0.07 geD RTN3 5.4 19.7 0.1 0.18 geD FCGR3B 6.5 23.6 0.12 0.12

APPENDIX J

TABLE S10 CR-specific measurements DataType Name Fold-change Q-value phenoD CD8 CENTRAL MEMORY 2.1 0.06 phenoD B CELLS 1.5 0.12 phenoD CD4 EFFECTOR MEMORY −2.7 0.12 phenoD NK T CELLS −2.6 0.12 phenoD CD4 −6.5 0.15 geD CD99L2 2.2 0 geD HSPD1 −1.4 0.01 geD SRF 1.7 0.02 geD BOK 2.5 0.02 geD LRP10 2.8 0.02 geD UBE2I 1.7 0.02 geD PANX1 1.7 0.02 geD NFKBIB 1.4 0.02 geD BLK 1.6 0.02 geD RAB5C 1.8 0.02 geD MKL1 1.7 0.02 geD NFKB2 1.5 0.02 geD SMAD7 1.6 0.02 geD IGF1 1.5 0.02 geD NR3C1 1.5 0.02 geD ITGA2B 1.4 0.02 geD C1R 2.2 0.02 geD BOC 1.4 0.02 geD CLSTN3 2 0.02 geD NISCH 2.6 0.02 geD SP1 1.6 0.02 geD PI4KB 2.2 0.02 geD PML 1.6 0.02 geD LAMA5 1.8 0.02 geD TNFSF10 2.4 0.02 geD MUC5AC 1.6 0.02 geD RAG1AP1 2.2 0.02 geD LILRA4 1.4 0.02 geD CLN3 1.7 0.02 geD CD40 2.1 0.02 geD AGPAT2 1.6 0.02 geD RAF1 1.8 0.02 geD EDN1 1.5 0.02 geD FEZ2 1.9 0.02 geD SART3 1.8 0.02 geD POGK 1.8 0.02 geD PXN 1.4 0.02 geD HIVEP2 2.3 0.02 geD NEK6 1.9 0.02 geD IGKC 1.6 0.02 geD SECTM1 1.7 0.02 geD FCN1 1.5 0.02 geD GRB2 1.4 0.02 geD PPP1R15A 2 0.02 geD GPX4 1.3 0.02 geD MAMDC4 1.6 0.02 geD SOCS7 2.3 0.02 geD COL9A1 1.7 0.02 geD TLR9 1.5 0.02 geD PTK2B 1.8 0.02 geD CLDN7 1.8 0.02 geD RHOA 1.6 0.02 geD NOXA1 1.5 0.02 geD PLAU 2.5 0.02 geD MLL3 1.6 0.02 geD TNNI2 1.8 0.02 geD FKBP14 1.6 0.02 geD AKT1 1.4 0.02 geD THBS3 1.7 0.02 geD PCDHA5 2.1 0.02 geD F8 1.5 0.02 geD CDKN2A 1.4 0.02 geD LIN7C 1.5 0.02 geD APOA1 1.6 0.02 geD DYRK2 1.3 0.02 geD KIF13B 1.7 0.02 geD CCR5 1.5 0.02 geD DAXX 1.7 0.02 geD WNK2 1.6 0.02 geD CD52 1.5 0.02 geD ALCAM 1.8 0.02 geD CISH 1.4 0.02 geD TLX2 1.8 0.02 geD AHSG 1.7 0.02 geD AGGF1 3.3 0.02 geD CREBBP 1.8 0.02 geD CDKN2C 1.7 0.02 geD GAPVD1 1.5 0.02 geD FGB 1.5 0.02 geD TNIP2 1.3 0.02 geD TMEM8 1.4 0.02 geD F5 1.9 0.02 geD SART1 1.8 0.02 geD NOS3 1.5 0.02 geD PSMG3 1.3 0.02 geD MCL1 2.1 0.02 geD PPARG 2.1 0.02 geD NEO1 1.9 0.02 geD TRPC4AP 1.6 0.02 geD CRYAB 1.5 0.02 geD CX3CL1 1.7 0.02 geD FOS 1.5 0.02 geD FOXC1 1.4 0.02 geD ICAM1 1.8 0.02 geD SRC 3.6 0.02 geD VAMP7 1.7 0.02 geD BYSL 1.3 0.02 geD CNTROB 1.4 0.02 geD BAK1 1.4 0.02 geD BBS9 1.4 0.02 geD PRKRIR 1.6 0.02 geD POLL 2.1 0.02 geD CLOCK −2.3 0.02 geD HCFC1 −2.8 0.02 geD CAV1 −1.6 0.02 geD MALT1 −2.2 0.02 geD TOX −1.9 0.02 geD ITGAE −2.2 0.02 geD CD1E −2 0.02 geD CDKN1B −1.3 0.02 geD SPP1 −2 0.02 geD IL18 −5.8 0.02 geD BRCA1 −3.3 0.02 geD NAE1 −3.1 0.02 geD PDCD6IP −2.5 0.02 geD RAB4A −1.5 0.02 geD GLO1 −2.2 0.02 geD PDCD5 −1.8 0.02 geD CD8A −2.1 0.02 geD HIF1A −1.6 0.02 geD ATP6V1H −1.4 0.02 geD EDNRB −1.8 0.02 geD IGFBP3 −2.9 0.02 geD FER −1.9 0.02 geD PTK2 −2.4 0.02 geD MIA3 −2.4 0.02 geD FNBP1 −1.4 0.02 geD SBDS −1.9 0.02 geD SLFN12 −2.8 0.02 geD RAB3B −3 0.02 geD PTPRC −2.4 0.02 geD PTGIS −1.8 0.02 geD STXBP5 −1.4 0.02 geD HIF1A −2.1 0.02 geD TOP1 −2 0.02 geD TBP −2.3 0.02 geD SMAD4 −2.8 0.02 geD SEMA6A −2 0.02 geD PPFIBP1 −1.6 0.02 geD MSH3 −1.7 0.02 geD PCNA −1.5 0.02 geD KLRC2 −2.1 0.02 geD SELS −2.4 0.02 geD LAMA4 −2.3 0.02 geD ADAT1 −2.2 0.02 geD MCTS1 −2.1 0.02 geD CD69 −2.4 0.02 geD ADAM10 −2.6 0.02 geD CLEC4A −2 0.02 geD ERCC4 −4.5 0.02 geD CARD16 −4.3 0.02 geD CLDN1 −2 0.02 geD SYNJ1 −1.9 0.02 geD UACA −1.7 0.02 geD EGR1 −2.1 0.02 geD FN1 −3.9 0.02 geD PRKAR2A −1.6 0.02 geD ESR1 −1.8 0.02 geD PSME3 −1.9 0.02 geD CEACAM6 −1.6 0.02 geD DOCK11 −1.7 0.02 geD PSMD1 −2.6 0.02 geD CD247 −1.3 0.02 geD CASK −1.7 0.02 geD LIG4 −2.1 0.02 geD GCNT2 −2.5 0.02 geD ADARB1 −1.7 0.02 geD SNX3 −1.9 0.02 geD DGCR2 −1.6 0.02 geD FKBP3 −1.8 0.02 geD CD59 −1.7 0.02 geD XRCC2 −1.9 0.02 geD RND3 −1.5 0.02 geD RAB5A −1.9 0.02 geD PSMD12 −2 0.02 geD LAMC1 −2.3 0.02 geD ZEB2 −2.2 0.02 geD ID2 −1.4 0.02 geD SLC23A2 −2 0.02 geD PTPN22 −1.5 0.02 geD HINT1 −2.2 0.02 geD STAT3 −1.9 0.02 geD MCL1 −1.8 0.02 geD FERMT2 −1.9 0.02 geD PVRL3 −2 0.02 geD PTGS2 −2.5 0.02 geD GAPVD1 −6.3 0.02 geD BFAR −2.6 0.02 geD PDIA3 −1.6 0.02 geD PACSIN2 −2.5 0.02 geD ITCH −1.6 0.02 geD SPOCK1 −1.3 0.02 geD TNFRSF1A −1.5 0.02 geD PTPN1 −2.1 0.02 geD BUB3 −1.9 0.02 geD MYC −1.8 0.02 geD PRKRA −1.5 0.02 geD PDCD2L −1.9 0.02 geD EFEMP1 −1.6 0.02 geD IRS1 −1.4 0.02 geD IFT81 −1.8 0.02 geD PKP3 1.8 0.03 geD IL1RN 1.7 0.03 geD SUMO1 1.3 0.03 geD CASP10 1.6 0.03 geD C3AR1 1.6 0.03 geD ZFP36 1.5 0.03 geD CD5 1.7 0.03 geD PEX5 1.4 0.03 geD DGKZ 2.3 0.03 geD BCL2L1 1.3 0.03 geD NUPR1 1.9 0.03 geD COL6A2 1.7 0.03 geD ACTN4 2 0.03 geD AMOTL1 1.5 0.03 geD GPR77 1.5 0.03 geD TCL1A 1.3 0.03 geD PSEN1 1.4 0.03 geD ELMO2 1.8 0.03 geD LTBP2 1.6 0.03 geD SDK1 1.7 0.03 geD CYBA 1.5 0.03 geD NTSR1 1.6 0.03 geD ITGB3BP 1.6 0.03 geD TAPBP 1.8 0.03 geD HOXB7 1.8 0.03 geD GDF5 1.6 0.03 geD NOG 1.5 0.03 geD NF1 1.6 0.03 geD CD163L1 1.9 0.03 geD HLA-A 1.3 0.03 geD PHF17 1.3 0.03 geD MGMT 1.6 0.03 geD ROBO3 1.3 0.03 geD HLA-C 1.7 0.03 geD BAX 1.5 0.03 geD FOXJ1 1.5 0.03 geD IFI27 3 0.03 geD MAPK14 1.6 0.03 geD CLN3 1.5 0.03 geD EGF 1.6 0.03 geD PARVB 1.6 0.03 geD CAPN10 2 0.03 geD TERT 1.6 0.03 geD PLAGL1 1.4 0.03 geD IGFALS 1.6 0.03 geD CFLAR 1.6 0.03 geD HDACS 1.2 0.03 geD ERBB2 2.3 0.03 geD RRAD 1.8 0.03 geD RPS3 1.8 0.03 geD ULBP2 1.8 0.03 geD CSF2RB 1.3 0.03 geD GHRL 1.7 0.03 geD CUTA 2 0.03 geD SIRPA 1.7 0.03 geD TP53AIP1 2 0.03 geD GMDS 1.8 0.03 geD HMOX1 2.4 0.03 geD TNFRSF10B 1.6 0.03 geD CLDN19 1.8 0.03 geD GP9 1.6 0.03 geD TRAF1 7.7 0.03 geD TGFB1I1 1.7 0.03 geD CHRNB2 2.4 0.03 geD CFHR1 1.3 0.03 geD ACIN1 1.4 0.03 geD AQP1 1.7 0.03 geD ADRM1 1.8 0.03 geD FANCC 2.1 0.03 geD IL18BP 1.5 0.03 geD INHBA 1.5 0.03 geD LIF 1.5 0.03 geD ARHGAP1 1.3 0.03 geD SOD1 1.5 0.03 geD TGFB1 1.4 0.03 geD NRP2 2 0.03 geD GATA2 1.9 0.03 geD NLRP1 1.5 0.03 geD FOLR1 1.6 0.03 geD WDR59 2.6 0.03 geD CD33 1.5 0.03 geD HRAS 1.8 0.03 geD DAD1 1.6 0.03 geD WDR92 2.2 0.03 geD PRKAR1B 1.9 0.03 geD MYC 1.6 0.03 geD MKNK2 1.4 0.03 geD IGF2BP2 1.8 0.03 geD CCR10 1.7 0.03 geD SECTM1 1.3 0.03 geD SDF4 1.4 0.03 geD RAMP3 1.4 0.03 geD TIAM1 1.3 0.03 geD SMAD2 −2.4 0.03 geD DERL1 −2.2 0.03 geD FASTKD1 −1.8 0.03 geD UTP11L −1.8 0.03 geD PTX3 −2.3 0.03 geD ITGB8 −1.5 0.03 geD ACVR1 −2 0.03 geD MDM4 −2 0.03 geD GSR −1.6 0.03 geD TERF1 −1.5 0.03 geD SCYE1 −2.2 0.03 geD C5 −2.1 0.03 geD MAP3K5 −1.7 0.03 geD EXOC5 −1.6 0.03 geD LRIG3 −2.1 0.03 geD FLRT2 −2.6 0.03 geD HIPK2 −1.6 0.03 geD C2CD2 −1.8 0.03 geD NFE2L3 −2.6 0.03 geD HIVEP1 −2.4 0.03 geD SCYE1 −1.6 0.03 geD DCTN3 −3.4 0.03 geD TDGF1 −1.4 0.03 geD C1QTNF3 −3.2 0.03 geD PDCD4 −2.2 0.03 geD HRH1 −2.4 0.03 geD ILK −3.1 0.03 geD CXCL3 −3.3 0.03 geD FLI1 −1.6 0.03 geD M6PR −1.7 0.03 geD JAK1 −1.3 0.03 geD SLC1A2 −2.1 0.03 geD BCL2 −1.8 0.03 geD ADH5 −2.7 0.03 geD CD46 −2.3 0.03 geD AKAP11 −1.4 0.03 geD APOH −1.5 0.03 geD PAFAH1B1 −1.7 0.03 geD ROCK2 −1.4 0.03 geD SEMA3A −1.7 0.03 geD CEACAM1 −1.7 0.03 geD NPHP4 −2.2 0.03 geD MDM2 −1.4 0.03 geD SP1 −1.5 0.03 geD LIMS1 −3.1 0.03 geD DCBLD2 −1.5 0.03 geD CSE1L −1.2 0.03 geD PKP2 −1.9 0.03 geD E2F2 −1.3 0.03 geD SEMA3A −1.8 0.03 geD PAFAH1B2 −1.8 0.03 geD PLDN −2.2 0.03 geD HIP1 −1.6 0.03 geD GDF6 −1.9 0.03 geD SH3KBP1 −1.7 0.03 geD THAP2 −2.7 0.03 geD RPS3A −2 0.03 geD ADAL −1.5 0.03 geD MTMR3 −2.4 0.03 geD MBD4 −1.5 0.03 geD SLC26A6 −1.5 0.03 geD PRKAR1A −1.5 0.03 geD PDLIM5 −1.9 0.03 geD PDLIM5 −1.7 0.03 geD STAT3 −1.5 0.03 geD DYRK2 −1.4 0.03 geD PSMC6 −2.1 0.03 geD MLLT11 −1.7 0.03 geD MPZL3 −1.6 0.03 geD MAGED1 −1.3 0.03 geD SERPINB9 −1.6 0.03 geD SERPINB2 −2.1 0.03 geD MLLT3 −1.5 0.03 geD AQP1 −1.4 0.03 geD RPS6KA3 −1.6 0.03 geD MYO6 −2.5 0.03 geD C2 −1.8 0.03 geD EEF1A1 −1.4 0.03 geD ROCK2 −1.6 0.03 geD CCR9 −2 0.03 geD PSMG2 −4.4 0.03 geD FGB −1.6 0.03 geD PML −2 0.03 geD SMNDC1 −1.4 0.03 geD HIVEP3 5.2 0.04 geD PARVG 1.5 0.04 geD MAPK8 1.8 0.04 geD CD3D 1.6 0.04 geD HDAC5 1.7 0.04 geD FXYD5 1.9 0.04 geD CDH23 1.7 0.04 geD PPT1 3.9 0.04 geD ZNF346 1.4 0.04 geD CIAPIN1 1.5 0.04 geD TRIM69 1.7 0.04 geD COL18A1 1.6 0.04 geD MLLT1 1.6 0.04 geD METTL11A 1.4 0.04 geD SIRPA 1.5 0.04 geD CXCL12 1.3 0.04 geD TMBIM6 2 0.04 geD MLLT1 1.2 0.04 geD IFI6 1.5 0.04 geD HSPA5 1.7 0.04 geD KCNH3 1.5 0.04 geD COL14A1 1.5 0.04 geD IMPDH1 1.6 0.04 geD TNFRSF18 2.1 0.04 geD SFRS17A 1.4 0.04 geD MPL 1.9 0.04 geD RRAGC 1.7 0.04 geD HPS4 1.8 0.04 geD MUC2 1.3 0.04 geD CD276 2.1 0.04 geD IRAK1 4.5 0.04 geD PRKD2 1.5 0.04 geD CDH10 2.2 0.04 geD DAB2 1.8 0.04 geD CYBB 1.4 0.04 geD B2M 1.2 0.04 geD ACTN1 1.5 0.04 geD PPM1D 1.9 0.04 geD C1orf38 1.5 0.04 geD ABL1 1.5 0.04 geD NOL3 1.5 0.04 geD C8A 1.6 0.04 geD HDAC1 2 0.04 geD LEFTY2 1.4 0.04 geD NCF1 2.2 0.04 geD TTYH1 2.1 0.04 geD AMICA1 2.5 0.04 geD SLC26A6 1.8 0.04 geD FSTL1 1.9 0.04 geD AP2A2 1.6 0.04 geD BGLAP 1.9 0.04 geD CD6 2.9 0.04 geD FKBP15 1.8 0.04 geD FASTK 1.4 0.04 geD PTPN6 1.5 0.04 geD CMTM5 1.3 0.04 geD ELN 1.4 0.04 geD NLRP12 1.6 0.04 geD CLDN10 1.5 0.04 geD DAP 1.4 0.04 geD ADRM1 1.6 0.04 geD IFITM1 1.3 0.04 geD LAIR1 1.2 0.04 geD RP11-138L21.1 1.7 0.04 geD DDR1 1.8 0.04 geD RASSF5 1.7 0.04 geD DCTN3 2.6 0.04 geD FOXC1 1.6 0.04 geD LSP1 1.3 0.04 geD CSNK1E 1.5 0.04 geD CEBPB 1.7 0.04 geD RAB5C 2.2 0.04 geD EXOC6 1.9 0.04 geD CD68 1.4 0.04 geD TREML2 6.3 0.04 geD VAV1 1.7 0.04 geD SERPINB2 1.7 0.04 geD NME6 1.4 0.04 geD NFATC4 1.4 0.04 geD PSME3 1.3 0.04 geD HLA-DMA 1.4 0.04 geD ATP2A2 1.7 0.04 geD ADRA1B 1.9 0.04 geD CEBPA 2.1 0.04 geD LYL1 2.9 0.04 geD ACTN1 1.8 0.04 geD FCGBP 1.6 0.04 geD STXBP2 2.2 0.04 geD NLRP3 1.6 0.04 geD CFHR3 −2.3 0.04 geD SLK −2.6 0.04 geD AMIGO2 −2.9 0.04 geD UBE2N −1.6 0.04 geD ZFYVE16 −2.6 0.04 geD GLMN −2.5 0.04 geD PTCD2 −2.3 0.04 geD ID2 −1.9 0.04 geD ALG9 −1.7 0.04 geD NBN −1.5 0.04 geD AVEN −2.2 0.04 geD TIAL1 −1.6 0.04 geD ZEB2 −2.5 0.04 geD CTNNA1 −1.7 0.04 geD BBS7 −1.7 0.04 geD PIK3R1 −1.5 0.04 geD MYST4 −1.3 0.04 geD LEF1 −1.3 0.04 geD ARF6 −3.3 0.04 geD PANX1 −1.4 0.04 geD PTPN12 −2.2 0.04 geD CLSTN1 −2.8 0.04 geD IGF2 −2.1 0.04 geD HMCN1 −1.6 0.04 geD SLC1A1 −1.3 0.04 geD TRAT1 −4.3 0.04 geD HTATIP2 −1.5 0.04 geD IGBP1 −1.5 0.04 geD STK38L −1.6 0.04 geD RGMB −2.6 0.04 geD EXOC1 −1.6 0.04 geD FCHSD2 −1.5 0.04 geD 7-Sep −1.4 0.04 geD RALA −1.7 0.04 geD RHOT1 −1.5 0.04 geD ITGB1 −1.5 0.04 geD TOLLIP −2 0.04 geD ARNTL −1.4 0.04 geD BCAP29 −1.7 0.04 geD AHSG −1.5 0.04 geD EXOC8 −2.2 0.04 geD ADH5 −1.3 0.04 geD FAF2 −1.9 0.04 geD NOD1 −2.1 0.04 geD HPS4 −1.5 0.04 geD RICTOR −1.9 0.04 geD SGK1 −1.6 0.04 geD FOXC1 −1.5 0.04 geD PDCL3 −2.4 0.04 geD CD28 −1.9 0.04 geD FKBP5 −2.3 0.04 geD PTPRF −1.8 0.04 geD MSX2 −1.6 0.04 geD SEMA5A −2.1 0.04 geD PAG1 −2.1 0.04 geD BLNK −2.1 0.04 geD CCL3L3 −2.2 0.04 geD SMAD3 −2.6 0.04 geD IFT74 −2.7 0.04 geD LRP8 −1.4 0.04 geD MLLT3 −1.4 0.04 geD WWTR1 −1.7 0.04 geD DPP4 −2.3 0.04 geD SHISA5 −2.4 0.04 geD PRKAR2A −1.7 0.04 geD EREG −2.1 0.04 geD BLM −5.3 0.04 geD ANXA4 −2.5 0.04 geD GAPVD1 −1.7 0.04 geD NAIP −1.6 0.04 geD CORO1C −1.2 0.04 geD LOC731884 −1.8 0.04 geD CD2BP2 −1.8 0.04 geD SEMA3C −1.3 0.04 geD C11orf82 −2.4 0.04 geD EIF2AK3 −2.1 0.04 geD PRKCA −1.6 0.04 geD ROBO2 −1.4 0.04 geD TTYH1 1.9 0.05 geD CEBPA 1.2 0.05 geD IGJ 1.6 0.05 geD ACHE 1.3 0.05 geD MKNK2 1.2 0.05 geD NLRC3 1.5 0.05 geD BTBD9 1.7 0.05 geD COL6A2 1.6 0.05 geD FBF1 1.2 0.05 geD CLDN11 1.6 0.05 geD HIPK2 1.5 0.05 geD PPAP2A 1.5 0.05 geD CTNNB1 1.4 0.05 geD CECR2 1.5 0.05 geD BST1 1.6 0.05 geD PNN 1.9 0.05 geD PCDH24 1.4 0.05 geD NFE2L1 1.5 0.05 geD CCL23 1.6 0.05 geD GP1BB 1.7 0.05 geD N-PAC 2.2 0.05 geD CORO1A 1.4 0.05 geD LGALS12 1.6 0.05 geD CASP2 1.6 0.05 geD HLA-C 1.5 0.05 geD CCR3 1.4 0.05 geD IL23A 1.6 0.05 geD ANGPTL4 1.3 0.05 geD GATA2 2.9 0.05 geD PCDH1 1.7 0.05 geD DDIT4 1.4 0.05 geD RPH3AL 1.5 0.05 geD HSPA1A 1.3 0.05 geD RPS6KA1 1.4 0.05 geD TFPT 1.5 0.05 geD SIRT6 1.5 0.05 geD CHRNA7 1.7 0.05 geD TROAP 1.6 0.05 geD TAX1BP3 1.4 0.05 geD ADAM8 1.4 0.05 geD TNFRSF1B 1.6 0.05 geD CSNK2B 1.5 0.05 geD CD99 4.1 0.05 geD SERPINA1 1.7 0.05 geD RAC2 1.2 0.05 geD MAPK3 1.4 0.05 geD COL20A1 1.4 0.05 geD ASGR2 1.8 0.05 geD NFKBIL1 2.1 0.05 geD MXD1 1.4 0.05 geD NP 1.3 0.05 geD C1QTNF4 1.5 0.05 geD NPTN 1.4 0.05 geD IFI16 1.4 0.05 geD DBNL 1.6 0.05 geD MAMDC2 2.3 0.05 geD RHOB 1.5 0.05 geD PCDHB13 1.6 0.05 geD ADAM33 1.8 0.05 geD IKBKB 1.5 0.05 geD ORM2 1.5 0.05 geD MLXIPL 1.4 0.05 geD PRSS2 2.6 0.05 geD DEDD2 1.4 0.05 geD GNL1 1.2 0.05 geD TGFBR1 1.6 0.05 geD VPREB1 1.4 0.05 geD CD320 1.5 0.05 geD HLA-C 1.5 0.05 geD ITIH1 1.8 0.05 geD NEDD4L 1.3 0.05 geD PCDHGA7 1.7 0.05 geD LY6E 1.8 0.05 geD TNFSF14 1.8 0.05 geD ACSF3 1.2 0.05 geD HLA-DQB1 1.6 0.05 geD IL17RA 1.5 0.05 geD FCN1 1.3 0.05 geD MLLT10 1.7 0.05 geD MFSD10 1.5 0.05 geD BAT3 1.6 0.05 geD IGHD 1.5 0.05 geD RABEP2 1.5 0.05 geD NLRC3 1.2 0.05 geD DGKA 1.6 0.05 geD ICAM2 1.4 0.05 geD VTN 1.4 0.05 geD RELB 1.6 0.05 geD PACSIN3 1.7 0.05 geD RAB3B 1.3 0.05 geD SMAD9 1.3 0.05 geD SIGLEC7 1.5 0.05 geD LTB 1.4 0.05 geD CD248 1.5 0.05 geD GSTA4 1.6 0.05 geD ACSF3 1.8 0.05 geD ITGA5 1.8 0.05 geD FOXO3 1.4 0.05 geD TSC22D3 1.3 0.05 geD CYTH2 1.9 0.05 geD MYST3 1.7 0.05 geD SDF2 1.5 0.05 geD F8 −1.8 0.05 geD SPARCL1 −1.6 0.05 geD DOCK3 −1.6 0.05 geD DST −1.5 0.05 geD NPM1 −1.8 0.05 geD AP1GBP1 −1.4 0.05 geD TNFAIP3 −1.6 0.05 geD ADH5 −1.8 0.05 geD GPR98 −1.3 0.05 geD CDH11 −2.3 0.05 geD BBS4 −1.7 0.05 geD SDCBP −2.3 0.05 geD C1QTNF3 −1.4 0.05 geD LRP12 −1.2 0.05 geD ICA1L −1.8 0.05 geD HTATIP2 −1.6 0.05 geD TRAF1 −1.6 0.05 geD CDH19 −1.6 0.05 geD RB1 −2.8 0.05 geD BIRC6 −1.5 0.05 geD BCL9 −1.3 0.05 geD THAP3 −1.7 0.05 geD CDC42 −1.7 0.05 geD SOD2 −1.6 0.05 geD LSM14A −1.4 0.05 geD CD302 −1.4 0.05 geD IL2RG −1.5 0.05 geD VCL −2.1 0.05 geD RIMS4 −2.2 0.05 geD FOXP1 −1.6 0.05 geD SNUPN −1.7 0.05 geD NME2 −2.6 0.05 geD SCARB2 −1.4 0.05 geD MAPK1 −1.2 0.05 geD PVR −1.8 0.05 geD 6-Sep −1.9 0.05 geD PRC1 −2 0.05 geD IKBKB −1.3 0.05 geD CLDN12 −1.8 0.05 geD NAMPT −1.9 0.05 geD ANGPTL1 −2.3 0.05 geD IFRD1 −2.8 0.05 geD RNF34 −1.8 0.05 geD MAP4K4 −1.5 0.05 geD TM2D1 −2.1 0.05 geD CASP8 −1.3 0.05 geD SRF −1.4 0.05 geD TERF1 −1.3 0.05 geD IFI16 −1.5 0.05 geD NDUFS1 −1.5 0.05 geD MIB1 −2 0.05 geD SDCBP −2 0.05 geD EP300 −2 0.05 geD NID1 −2 0.05 geD EYA1 −1.7 0.05 geD GPR126 −1.8 0.05 geD HDAC4 −1.4 0.05 geD SH2D1A −2.5 0.05 geD TLR3 −2.4 0.05 geD HSPA8 −1.6 0.05 geD CXADR −1.3 0.05 geD PFDN6 −1.4 0.05 geD SEMA4F −1.6 0.05 geD FAM3C −1.5 0.05 geD BMI1 −1.4 0.05 geD CD86 −2 0.05 geD GRAMD4 −1.7 0.05 geD HSP90AA1 −1.7 0.05 geD ANXA5 −1.5 0.05 geD PTGES3 −2.7 0.05 geD CAMK2D −2 0.05 geD IGSF5 −1.6 0.05 geD NCK2 1.4 0.06 geD KCNMA1 1.7 0.06 geD LOC442421 1.4 0.06 geD VPS45 1.3 0.06 geD CD81 1.3 0.06 geD CAMK1D 1.3 0.06 geD CALM3 1.8 0.06 geD BAX 1.3 0.06 geD HFE 1.6 0.06 geD CD96 1.7 0.06 geD NFATC2IP 1.4 0.06 geD MYH9 1.3 0.06 geD EEF1A2 1.6 0.06 geD MLF2 1.3 0.06 geD NAB2 1.4 0.06 geD BAT2 1.5 0.06 geD TNFSF12 1.7 0.06 geD PAK2 1.5 0.06 geD CES1 1.5 0.06 geD PAK1 1.5 0.06 geD KLF6 2.1 0.06 geD 5-Sep 1.5 0.06 geD GNA12 1.4 0.06 geD BIN3 1.5 0.06 geD C4BPB 1.9 0.06 geD ICAM3 1.3 0.06 geD SKAP2 1.6 0.06 geD HMCN2 1.5 0.06 geD PTPRU 1.3 0.06 geD COTL1 1.4 0.06 geD HLA-DPA1 1.3 0.06 geD TYROBP 1.3 0.06 geD PGP 1.7 0.06 geD LATS2 1.5 0.06 geD FKBP8 1.6 0.06 geD BSG 1.5 0.06 geD RPS6KA2 1.4 0.06 geD SCRN1 1.6 0.06 geD MLL 1.4 0.06 geD BID 1.6 0.06 geD TRBV5-4 1.4 0.06 geD FGFR1 1.5 0.06 geD PML 1.7 0.06 geD TRAF7 1.6 0.06 geD TLX2 1.4 0.06 geD DOCK5 2.4 0.06 geD HIST1H2AL 1.3 0.06 geD PKD1 1.3 0.06 geD NCF1 1.3 0.06 geD EIF5A 1.4 0.06 geD SPN 1.5 0.06 geD PECAM1 1.6 0.06 geD CSNK1E 1.3 0.06 geD CD19 1.8 0.06 geD FXYD5 1.3 0.06 geD 3-Mar 1.5 0.06 geD TIMP3 1.2 0.06 geD ADAM22 1.3 0.06 geD PYDC1 1.6 0.06 geD JAK1 1.4 0.06 geD RIN1 1.4 0.06 geD ADORA2A 1.5 0.06 geD CYFIP2 1.6 0.06 geD PURB 1.5 0.06 geD IFT172 1.3 0.06 geD FEZF2 1.3 0.06 geD PXN 1.7 0.06 geD CLDN5 1.6 0.06 geD HLA-B 1.6 0.06 geD MAP3K1 1.4 0.06 geD STAT5B 1.5 0.06 geD MR1 1.5 0.06 geD BIN1 1.3 0.06 geD PCDHGA2 1.2 0.06 geD STAT5A 1.3 0.06 geD ITFG2 1.5 0.06 geD LAMA5 1.3 0.06 geD RALBP1 1.6 0.06 geD IGHV1-69 1.6 0.06 geD GRN 1.4 0.06 geD PPM1F 1.7 0.06 geD NKD2 1.6 0.06 geD SFN 1.2 0.06 geD CLDN14 2.8 0.06 geD MARK3 1.6 0.06 geD GALNTL1 1.3 0.06 geD GADD45B 1.4 0.06 geD TNFRSF21 1.5 0.06 geD NLRP1 1.2 0.06 geD DDR1 1.5 0.06 geD NEIL2 1.2 0.06 geD CEACAM19 1.4 0.06 geD FLRT2 1.4 0.06 geD F2 1.3 0.06 geD IRF7 1.6 0.06 geD CD3EAP 1.3 0.06 geD FANCG 1.5 0.06 geD ADAR 1.5 0.06 geD RBM4 1.6 0.06 geD TCIRG1 1.4 0.06 geD NFATC3 1.3 0.06 geD CMKLR1 1.3 0.06 geD ITGB4 1.6 0.06 geD CPXM1 1.4 0.06 geD TMX1 1.6 0.06 geD ZFYVE9 1.3 0.06 geD PRKACA 1.6 0.06 geD UBE2Z 1.4 0.06 geD SPG7 1.6 0.06 geD RNF216 1.4 0.06 geD RIN3 1.4 0.06 geD SELPLG 1.9 0.06 geD NEIL3 −1.6 0.06 geD INHA −1.5 0.06 geD C3orf38 −1.4 0.06 geD IFNA4 −1.3 0.06 geD MLL3 −2 0.06 geD FAM3B −1.9 0.06 geD NFE2L3 −1.4 0.06 geD RALBP1 −2.2 0.06 geD FNBP1L −1.5 0.06 geD KLRF1 −1.6 0.06 geD COL14A1 −1.8 0.06 geD CKAP2 −1.6 0.06 geD ZNF443 −1.9 0.06 geD IGJ −1.5 0.06 geD CTNND1 −1.2 0.06 geD RAB18 −2 0.06 geD TXN −1.5 0.06 geD IRF4 −1.4 0.06 geD RPS3A −1.4 0.06 geD NFATC2 −2.4 0.06 geD RYBP −1.1 0.06 geD WNK1 −1.4 0.06 geD DOCK8 −1.6 0.06 geD DOCK5 −2 0.06 geD LRP12 −1.8 0.06 geD VEGFB −1.6 0.06 geD RPS3A −1.8 0.06 geD RAB27A −1.7 0.06 geD IL2RB −1.3 0.06 geD S100B −1.7 0.06 geD SLFN11 −1.3 0.06 geD FANCI −1.6 0.06 geD LCP1 −1.8 0.06 geD TRBV27 −1.6 0.06 geD DOCK7 −1.6 0.06 geD BNIP3L −1.8 0.06 geD BCL10 −1.3 0.06 geD VEZF1 −1.3 0.06 geD PDIA3 −1.5 0.06 geD FEZ1 −2.5 0.06 geD NGFRAP1 −1.4 0.06 geD TNFRSF17 −1.5 0.06 geD AGGF1 −2.2 0.06 geD PTPN22 −1.9 0.06 geD PCDHB15 −1.5 0.06 geD THRB −1.3 0.06 geD CARD6 −1.3 0.06 geD FAM82A2 −2 0.06 geD YWHAZ −1.3 0.06 geD GCLC −1.3 0.06 geD HFE −1.9 0.06 geD DNM1L −1.2 0.06 geD FCHO2 −1.8 0.06 geD IL20RB −1.7 0.06 geD KIR3DL3 −1.5 0.06 geD DLX1 −1.6 0.06 geD PAWR −1.8 0.06 geD FNDC3A −1.3 0.06 geD GYPA −1.3 0.06 geD IGLL1 −1.4 0.06 geD MYST3 −1.3 0.06 geD ITGA6 −1.8 0.06 geD IL1R1 −1.5 0.06 geD SCD5 −2.2 0.06 geD SGK3 −1.9 0.06 geD VEZF1 −1.9 0.06 geD SIX4 −1.2 0.06 geD FGFR1 −1.7 0.06 geD CMAS −1.4 0.06 geD FANCM −1.6 0.06 geD NDN −2.2 0.06 geD ABCC4 −1.6 0.06 geD PSMD3 5.5 0.07 geD BBC3 1.4 0.07 geD PARVA 1.5 0.07 geD ITGAL 1.3 0.07 geD XRCC6 2.2 0.07 geD BAI1 1.5 0.07 geD CBL 1.3 0.07 geD ITGAX 1.6 0.07 geD NPM1 1.4 0.07 geD MAP4K2 1.6 0.07 geD UNC5B 1.6 0.07 geD OSM 1.4 0.07 geD TNFRSF6B 1.6 0.07 geD TNIP1 1.4 0.07 geD IL6ST 1.6 0.07 geD XAF1 1.2 0.07 geD IL3RA 1.3 0.07 geD PKD1 1.4 0.07 geD MEN1 1.5 0.07 geD C1QTNF2 1.7 0.07 geD HDAC4 1.5 0.07 geD CX3CL1 1.8 0.07 geD FIS1 1.4 0.07 geD BMF 1.5 0.07 geD CDH18 1.6 0.07 geD PRDX2 1.2 0.07 geD FASTKD3 1.3 0.07 geD NFATC1 1.4 0.07 geD PCDHB11 1.3 0.07 geD CADM3 1.3 0.07 geD HCG18 1.4 0.07 geD TMBIM6 1.7 0.07 geD SDF2L1 1.2 0.07 geD ARRB2 1.4 0.07 geD OXSR1 1.3 0.07 geD AATK 1.6 0.07 geD MUC5AC 1.6 0.07 geD TNFRSF1A 1.6 0.07 geD CTSD 1.2 0.07 geD EXOC5 1.5 0.07 geD LOC644297 2.5 0.07 geD EMD 1.3 0.07 geD DNASE1L3 1.3 0.07 geD SIAH2 1.5 0.07 geD MYD88 1.5 0.07 geD PTGDS 1.2 0.07 geD NINJ1 1.6 0.07 geD TRIB3 1.4 0.07 geD MLL3 1.5 0.07 geD PCDH21 1.2 0.07 geD CLDN3 1.6 0.07 geD CD1A 1.3 0.07 geD FGF3 1.5 0.07 geD PECR 1.2 0.07 geD MSRA 2.6 0.07 geD CTSK 1.4 0.07 geD TAPBP 1.4 0.07 geD PCLO 1.4 0.07 geD LGALS1 1.1 0.07 geD GPR56 2.5 0.07 geD TRIP6 1.5 0.07 geD ASB1 1.4 0.07 geD TYK2 1.6 0.07 geD ELMO2 1.5 0.07 geD ENG 1.3 0.07 geD NFKBIB 1.6 0.07 geD NISCH 1.6 0.07 geD CMTM3 1.3 0.07 geD FN1 1.2 0.07 geD CDC2L2 1.6 0.07 geD FCGRT 1.3 0.07 geD COQ7 1.5 0.07 geD SMOC1 5.2 0.07 geD CAMP 1.5 0.07 geD DOCK6 2.4 0.07 geD SYTL1 1.5 0.07 geD EMR1 1.3 0.07 geD THY1 2.2 0.07 geD IFIT1 1.2 0.07 geD JAK3 1.5 0.07 geD UBL7 1.2 0.07 geD FOXL2 2.8 0.07 geD PLAUR 1.3 0.07 geD ROBO3 1.3 0.07 geD NLRP12 1.2 0.07 geD TBRG4 1.5 0.07 geD VEGFA 1.3 0.07 geD CDH3 2.1 0.07 geD CTNND2 1.4 0.07 geD CALM3 1.2 0.07 geD ISG20 1.2 0.07 geD MAP2K3 1.5 0.07 geD CSRNP2 1.6 0.07 geD HAX1 1.3 0.07 geD SMO 1.3 0.07 geD DAPK2 1.4 0.07 geD ALG1 1.5 0.07 geD IL11RA 1.1 0.07 geD MAF 1.6 0.07 geD ARHGDIA 1.3 0.07 geD THOC5 1.6 0.07 geD NPM1 2.6 0.07 geD PSMG2 −1.3 0.07 geD C1RL −2.6 0.07 geD C3orf38 −1.3 0.07 geD FANCD2 −1.4 0.07 geD MAP3K7 −1.5 0.07 geD RIMS3 −1.2 0.07 geD NLGN1 −1.5 0.07 geD ERBB4 −1.6 0.07 geD LIN7C −1.2 0.07 geD PHLDA2 −1.9 0.07 geD DIAPH2 −2.3 0.07 geD FANCD2 −2.1 0.07 geD FASTKD2 −1.9 0.07 geD NLGN4Y −1.5 0.07 geD PAG1 −1.9 0.07 geD SLC1A3 −2.2 0.07 geD BIRC2 −1.6 0.07 geD PSMD3 −1.5 0.07 geD CAPN10 −1.4 0.07 geD CXADR −1.8 0.07 geD POSTN −1.5 0.07 geD RNF34 −1.3 0.07 geD RABEP1 −1.3 0.07 geD GBP1 −1.5 0.07 geD ALG9 −2.5 0.07 geD PSMC5 −1.5 0.07 geD GULP1 −1.2 0.07 geD C9orf61 −1.2 0.07 geD CASP8 −1.6 0.07 geD NHEJ1 −1.4 0.07 geD MLH1 −1.4 0.07 geD ITPR1 −1.2 0.07 geD C7 −1.6 0.07 geD CROP −1.6 0.07 geD SMURF2 −1.9 0.07 geD LPP −1.3 0.07 geD HMGB1 −1.2 0.07 geD RABEP1 −1.5 0.07 geD PCDHA11 −1.3 0.07 geD CDC42SE2 −1.4 0.07 geD HLA-C −1.4 0.07 geD RAG1 −1.2 0.07 geD RHOT1 −1.3 0.07 geD HDAC4 −1.4 0.07 geD EXOC5 −1.8 0.07 geD ART4 −2.2 0.07 geD FANCI −1.4 0.07 geD WWTR1 −1.4 0.07 geD MAPK9 −1.6 0.07 geD PTK2 −1.4 0.07 geD COL14A1 −1.2 0.07 geD HNMT −1.3 0.07 geD LY75 −1.4 0.07 geD LYST −1.3 0.07 geD DOCK1 −1.3 0.07 geD MAF −2.2 0.07 geD PRKCB −1.5 0.07 geD TNFRSF11B −1.2 0.07 geD PSMD9 −1.5 0.07 geD PTGES3 −1.4 0.07 geD ALDH1A3 −1.7 0.07 geD TBRG1 −1.2 0.07 geD BAG3 −1.2 0.07 geD CCR6 −1.4 0.07 geD PSMD10 −1.3 0.07 geD ANLN −1.6 0.07 geD ALDH1A2 −1.8 0.07 geD PRKCSH 1.5 0.08 geD MZF1 1.3 0.08 geD AP3B2 1.7 0.08 geD SEMA6A 1.5 0.08 geD IL16 1.6 0.08 geD ITGAX 1.5 0.08 geD HLA-DPA1 8.8 0.08 geD CCND3 1.4 0.08 geD TGFB3 1.6 0.08 geD UCP2 1.4 0.08 geD LTBP3 1.4 0.08 geD WISP2 2.3 0.08 geD HLA-E 1.6 0.08 geD AOAH 1.4 0.08 geD F7 1.4 0.08 geD WFS1 1.3 0.08 geD ADAT3 1.3 0.08 geD SPON2 1.6 0.08 geD CLN3 1.2 0.08 geD PYCARD 1.3 0.08 geD HLA-DMA 1.3 0.08 geD LTBP4 1.2 0.08 geD DGCR8 1.3 0.08 geD ING4 1.4 0.08 geD IFI27L2 2.2 0.08 geD CFP 1.3 0.08 geD HDAC3 1.7 0.08 geD IRF2 2.3 0.08 geD MLLT1 1.3 0.08 geD APOL2 1.4 0.08 geD PTPRS 1.3 0.08 geD LST1 1.5 0.08 geD PCDHB2 1.3 0.08 geD BTNL2 1.5 0.08 geD TAPBPL 1.4 0.08 geD VPS33B 1.3 0.08 geD CDK5 1.5 0.08 geD HLA-DRB4 1.4 0.08 geD CDH7 1.4 0.08 geD AP1B1 1.3 0.08 geD PSMB9 1.7 0.08 geD HEPACAM 1.8 0.08 geD CD97 1.6 0.08 geD NFX1 1.2 0.08 geD EXOC4 1.4 0.08 geD PRDX2 1.4 0.08 geD AIFM2 1.6 0.08 geD ITGB6 1.5 0.08 geD FKBP9 1.6 0.08 geD TOM1 1.2 0.08 geD CLPTM1L 1.4 0.08 geD BIRC7 1.4 0.08 geD EPN2 1.9 0.08 geD PPIL2 1.6 0.08 geD TIMP2 6.7 0.08 geD RTN3 1.3 0.08 geD FKBP5 1.2 0.08 geD POU4F1 1.2 0.08 geD CMTM1 1.3 0.08 geD EBI3 1.4 0.08 geD LSM14A 1.3 0.08 geD IL8RB 1.2 0.08 geD MTCH1 1.3 0.08 geD BBS2 1.4 0.08 geD IFT122 1.4 0.08 geD LY6G6C 1.4 0.08 geD LTBP4 1.1 0.08 geD DOCK2 1.3 0.08 geD MX1 1.3 0.08 geD INHBB 1.2 0.08 geD EMILIN1 1.4 0.08 geD MLL4 1.1 0.08 geD TYMP 1.3 0.08 geD ZYX 1.3 0.08 geD CLDN3 1.4 0.08 geD PRKG1 1.7 0.08 geD SPACA3 1.3 0.08 geD ADAMTS1 −1.3 0.08 geD DCBLD1 −1.7 0.08 geD PAFAH1B1 −1.5 0.08 geD CD164 −1.7 0.08 geD HBP1 −1.3 0.08 geD PHLPP −1.8 0.08 geD XRCC6BP1 −1.3 0.08 geD SNX6 −1.5 0.08 geD ELMOD1 −1.6 0.08 geD AP1G1 −1.2 0.08 geD DNAJB6 −1.3 0.08 geD SYVN1 −1.8 0.08 geD IKBKAP −1.5 0.08 geD RPS6KA3 −1.3 0.08 geD CD63 −1.3 0.08 geD USP33 −1.5 0.08 geD BCLAF1 −1.5 0.08 geD TNFAIP8L1 −1.3 0.08 geD PVRL3 −1.6 0.08 geD UBE2N −1.5 0.08 geD DST −1.4 0.08 geD SLK −1.4 0.08 geD 4-Sep −1.4 0.08 geD BMI1 −1.9 0.08 geD PTGR2 −1.4 0.08 geD PTEN −1.7 0.08 geD KCNMA1 −1.5 0.08 geD PROX1 −1.6 0.08 geD GALNAC4S-6ST −1.4 0.08 geD TOP2A −1.6 0.08 geD RAB22A −1.4 0.08 geD LAMP2 −1.2 0.08 geD RNF144B −1.2 0.08 geD STX1A −1.6 0.08 geD PLDN −1.2 0.08 geD PSME3 −1.6 0.08 geD GNA13 −1.3 0.08 geD NXT2 −1.7 0.08 geD COL8A1 −1.3 0.08 geD DOCK4 −1.2 0.08 geD SYNJ2BP −1.4 0.08 geD RPS3A −2 0.08 geD NBN −1.6 0.08 geD PIM1 −1.3 0.08 geD FLT1 −1.4 0.08 geD UCHL1 −1.4 0.08 geD KLRG1 −1.6 0.08 geD API5 −1.8 0.08 geD RRAGC −1.3 0.08 geD MBL2 −1.3 0.08 geD MATN3 −1.8 0.08 geD COL14A1 −1.2 0.08 geD CADM1 −1.7 0.08 geD ADAM12 −1.7 0.08 geD B2M −1.5 0.08 geD RBPJ −1.3 0.08 geD SHISA5 1.3 0.09 geD FRAT2 1.2 0.09 geD PCDHB8 1.5 0.09 geD ADRBK1 1.2 0.09 geD ZNF646 1.4 0.09 geD PARD3 1.3 0.09 geD DCTN3 1.4 0.09 geD EBF4 1.3 0.09 geD CERK 1.4 0.09 geD POLM 1.3 0.09 geD PTPN11 1.3 0.09 geD PTGIR 1.4 0.09 geD FLVCR1 1.2 0.09 geD CD2BP2 1.3 0.09 geD PDCD1 1.6 0.09 geD BGLAP 1.6 0.09 geD ATHL1 1.5 0.09 geD SAP30BP 1.6 0.09 geD CLU 1.5 0.09 geD THBS4 1.4 0.09 geD MST1R 1.8 0.09 geD NFKBIL2 1.4 0.09 geD RECQL4 1.8 0.09 geD FUT4 1.3 0.09 geD AIF1 1.2 0.09 geD PTK7 1.3 0.09 geD CEACAM4 2.5 0.09 geD C1orf38 1.5 0.09 geD JUP 1.4 0.09 geD OSCAR 1.7 0.09 geD BCAP31 1.5 0.09 geD COL8A1 1.2 0.09 geD CAMK1G 2.6 0.09 geD FGFR3 1.4 0.09 geD CSF2RA 1.5 0.09 geD GAS1 1.4 0.09 geD TH1L 1.8 0.09 geD ICAM5 1.6 0.09 geD SHISA5 1.9 0.09 geD FIS1 1.3 0.09 geD LAG3 1.4 0.09 geD FGFR1 1.2 0.09 geD SPHK2 1.3 0.09 geD NRXN2 1.5 0.09 geD NPHP1 1.4 0.09 geD IL1R1 1.4 0.09 geD ABL1 1.2 0.09 geD RHOA 1.6 0.09 geD MLLT6 1.6 0.09 geD PLD1 1.4 0.09 geD WNK1 1.6 0.09 geD ZNF3 1.5 0.09 geD LST1 1.5 0.09 geD IL21R 3.9 0.09 geD TGM2 3.4 0.09 geD DNASE2 1.7 0.09 geD FCRL2 1.3 0.09 geD LILRA1 1.6 0.09 geD RAB35 1.4 0.09 geD MYH10 1.1 0.09 geD MAPK11 1.3 0.09 geD APOE 1.4 0.09 geD DOK1 1.5 0.09 geD CELSR3 1.3 0.09 geD BUB1B 1.5 0.09 geD GLT25D2 1.4 0.09 geD PRAM1 1.6 0.09 geD SLC4A1 1.4 0.09 geD SMAD6 1.3 0.09 geD ERBB3 1.4 0.09 geD OLFML3 1.4 0.09 geD HLA-E 1.3 0.09 geD LSM14B 1.2 0.09 geD KNG1 1.5 0.09 geD FBLIM1 1.2 0.09 geD CSF3R 1.2 0.09 geD AP2A1 1.6 0.09 geD SEMA3F 1.4 0.09 geD ANP32D 1.3 0.09 geD PBX2 1.4 0.09 geD CD74 1.5 0.09 geD CSNK2B 1.3 0.09 geD SYNJ1 1.3 0.09 geD VHL 1.3 0.09 geD HLA-G 1.7 0.09 geD WFIKKN1 1.3 0.09 geD MED1 −1.8 0.09 geD GNA13 −1.3 0.09 geD PDCD2 −1.4 0.09 geD STK17A −1.3 0.09 geD NPM1 −1.4 0.09 geD ROCK1 −1.4 0.09 geD PCDH8 −1.7 0.09 geD RABGEF1 −1.4 0.09 geD SP3 −1.7 0.09 geD AP1S3 −1.6 0.09 geD PIK3CB −1.2 0.09 geD C8orf4 −1.6 0.09 geD UBR1 −1.5 0.09 geD HES1 −1.3 0.09 geD CARD8 −1.3 0.09 geD RTN4 −1.4 0.09 geD ALB −1.7 0.09 geD TERF1 −1.7 0.09 geD RHD −1.4 0.09 geD MLLT10 −1.6 0.09 geD ROCK1 −1.5 0.09 geD CDC42 −1.3 0.09 geD MAP4K5 −1.8 0.09 geD HSP90B1 −1.2 0.09 geD CFLAR −1.7 0.09 geD PPIL4 −1.8 0.09 geD MICB −1.4 0.09 geD CD109 −1.8 0.09 geD LYAR −1.7 0.09 geD PSMC6 −1.4 0.09 geD MSN −2.2 0.09 geD NRAS −1.3 0.09 geD CFI −1.2 0.09 geD TERF1 −1.7 0.09 geD DYRK2 −1.7 0.09 geD RAD21 −2 0.09 geD BMI1 −1.3 0.09 geD LAMP2 −1.4 0.09 geD CFDP1 −1.3 0.09 geD PTEN −2.2 0.09 geD PCDH7 −1.5 0.09 geD PTGS1 −1.8 0.09 geD PPARGC1A −1.7 0.09 geD MARCKS −2.1 0.09 geD GPNMB −1.7 0.09 geD DNAJB6 −1.6 0.09 geD LAMP2 −1.5 0.09 geD RICTOR −1.1 0.09 geD CORO1C −1.5 0.09 geD DAD1 −1.3 0.09 geD SDF2 −1.4 0.09 geD PTGER4 −1.6 0.09 geD MLLT4 1.1 0.1 geD ASGR1 1.2 0.1 geD VTCN1 1.6 0.1 geD CXCL14 1.3 0.1 geD SNX3 1.4 0.1 geD MLLT6 2.1 0.1 geD TNFSF13 1.2 0.1 geD ERCC1 1.3 0.1 geD DLL3 1.5 0.1 geD IRGC 1.3 0.1 geD CD36 1.3 0.1 geD C16orf5 1.2 0.1 geD PAFAH1B3 1.2 0.1 geD CDC2L1 1.6 0.1 geD CALY 1.3 0.1 geD ZNF646 1.3 0.1 geD AZGP1 1.3 0.1 geD CUBN 1.6 0.1 geD EEF1A1 1.2 0.1 geD SHB 1.2 0.1 geD PSMF1 2.8 0.1 geD DDX41 1.2 0.1 geD PI4KB 1.3 0.1 geD PCDHB7 1.3 0.1 geD GPR126 1.3 0.1 geD MFAP4 1.2 0.1 geD ELMOD3 1.4 0.1 geD CYP26A1 1.4 0.1 geD XRCC3 1.4 0.1 geD SERPINA3 1.3 0.1 geD TP53INP1 1.3 0.1 geD PRKCQ 1.3 0.1 geD RFX2 1.4 0.1 geD NCOA6 1.6 0.1 geD DSCAM 1.4 0.1 geD AZU1 1.4 0.1 geD TRAF5 1.3 0.1 geD NTN1 1.4 0.1 geD CCL27 1.2 0.1 geD CLCF1 1.3 0.1 geD IRS2 1.3 0.1 geD IER3 1.3 0.1 geD PML 1.2 0.1 geD SLPI 1.9 0.1 geD LMNA 1.3 0.1 geD ACVRL1 1.2 0.1 geD PACS2 1.4 0.1 geD TAPBP 1.3 0.1 geD LTBP2 1.4 0.1 geD MICB 1.2 0.1 geD PVR 1.5 0.1 geD MADCAM1 1.2 0.1 geD TRIM35 1.2 0.1 geD RAB7A 1.2 0.1 geD HEPACAM 1.3 0.1 geD TOLLIP 1.2 0.1 geD MYO18A 1.4 0.1 geD VCP 1.5 0.1 geD NGFR 1.4 0.1 geD BSG 1.2 0.1 geD COL15A1 1.4 0.1 geD BAT4 1.7 0.1 geD MYST1 2.6 0.1 geD MAST1 1.3 0.1 geD PBX4 1.6 0.1 geD FLNA 1.2 0.1 geD MALL 1.2 0.1 geD IL8RB 1.3 0.1 geD HCG18 1.6 0.1 geD PVRIG 1.2 0.1 geD CCL15 1.2 0.1 geD AREG 1.4 0.1 geD CCL16 1.3 0.1 geD CEACAM7 1.4 0.1 geD CHST10 1.2 0.1 geD VEGFB 1.4 0.1 geD TNFRSF8 1.2 0.1 geD ADAT2 1.4 0.1 geD CHRD 1.4 0.1 geD ROM1 1.1 0.1 geD SHFM1 −1.3 0.1 geD TOR1AIP2 −1.2 0.1 geD ATP1A2 −1.4 0.1 geD PCMT1 −1.4 0.1 geD CP110 −2.1 0.1 geD RGN −1.7 0.1 geD PICALM −2.3 0.1 geD FANCB −1.3 0.1 geD ZNF675 −1.6 0.1 geD IBTK −1.3 0.1 geD CCAR1 −1.6 0.1 geD YWHAZ −1.3 0.1 geD ATP2A2 −1.5 0.1 geD HTATSF1 −1.4 0.1 geD NR4A1 −1.9 0.1 geD CREB1 −1.3 0.1 geD KYNU −1.3 0.1 geD CRKL −1.3 0.1 geD STON1 −1.3 0.1 geD MSN −1.3 0.1 geD MLL3 −1.6 0.1 geD MIA3 −1.5 0.1 geD FANCF −2.2 0.1 geD CXADR −1.3 0.1 geD ADAR −1.6 0.1 geD RP6-213H19.1 −1.6 0.1 geD TOP2B −1.3 0.1 geD FASTKD2 −1.2 0.1 geD PRKAR2B −1.5 0.1 geD CXCL1 −1.9 0.1 geD PSMC1 −1.2 0.1 geD LOC442421 −1.8 0.1 geD COL29A1 −1.4 0.1 geD NFAT5 −1.2 0.1 geD DLEU2 −1.5 0.1 geD SRFBP1 −1.3 0.1 geD ITGAV −1.4 0.1 geD ELF1 −1.4 0.1 geD HBP1 −1.6 0.1 geD KCNIP3 −1.3 0.1 geD ICK −1.2 0.1 geD EXOC6B −1.8 0.1 geD PCDHB9 −1.6 0.1 geD TNFRSF19 −1.2 0.1 geD ZMYM2 −1.1 0.1 geD COPG2 −1.3 0.1 geD DLC1 −1.2 0.1 geD ACVR1C −1.2 0.1 geD ATR −1.2 0.1 geD UBE4B −1.5 0.1 geD CAMK2D −1.3 0.1 geD IL16 −1.7 0.1 geD BECN1 −1.2 0.1 geD COL13A1 −1.9 0.1 geD BIRC3 −1.5 0.1 geD CD55 −1.3 0.1 geD UTP14A −1.5 0.1 geD PPT1 −1.3 0.1 geD GNA12 1.3 0.11 geD LTBR 1.3 0.11 geD NFKBIE 1.4 0.11 geD IL15RA 1.3 0.11 geD SCARB1 1.4 0.11 geD RAB26 1.3 0.11 geD C1QTNF6 1.3 0.11 geD EMILIN2 1.1 0.11 geD BICD2 1.6 0.11 geD ITFG2 1.3 0.11 geD CD97 1.6 0.11 geD BBC3 1.3 0.11 geD LOC91316 1.9 0.11 geD FOXO3 1.2 0.11 geD GPX1 3.6 0.11 geD OLFML3 1.4 0.11 geD CBX4 1.4 0.11 geD ERBB3 1.4 0.11 geD GPR17 1.3 0.11 geD INHBC 2.7 0.11 geD ARHGEF11 1.2 0.11 geD PRDX1 1.9 0.11 geD SNX17 1.3 0.11 geD RYBP 1.3 0.11 geD PNN 2.5 0.11 geD CLDN9 1.4 0.11 geD IL3RA 1.2 0.11 geD TNFRSF10B 1.2 0.11 geD ADORA2A 1.3 0.11 geD ACOX1 1.3 0.11 geD IL10RA 1.2 0.11 geD FKBP1A 1.5 0.11 geD IFI27L1 2 0.11 geD PTAFR 2.5 0.11 geD GDF15 1.1 0.11 geD CARD17 1.8 0.11 geD YKT6 1.4 0.11 geD ADAM12 1.2 0.11 geD MYST4 1.3 0.11 geD RPS6KA5 9.5 0.11 geD BBS7 1.3 0.11 geD CXCL5 1.3 0.11 geD COL16A1 1.3 0.11 geD CYTL1 1.2 0.11 geD FBLIM1 1.6 0.11 geD COL6A1 1.1 0.11 geD TNFRSF4 1.4 0.11 geD SYVN1 1.4 0.11 geD CD300C 1.3 0.11 geD TCTA 1.3 0.11 geD CCL17 1.3 0.11 geD PSMD9 1.6 0.11 geD EPOR 1.3 0.11 geD ERCC3 1.3 0.11 geD IGF2BP3 1.5 0.11 geD PEX5 1.4 0.11 geD RIMS4 1.5 0.11 geD PPIH 1.2 0.11 geD NAB2 1.3 0.11 geD EXOC4 −1.3 0.11 geD RHCE −1.3 0.11 geD SGMS1 −1.4 0.11 geD PSMD12 −1.2 0.11 geD SNAP29 −1.5 0.11 geD DLG1 −1.3 0.11 geD FEN1 −1.5 0.11 geD TTRAP −1.2 0.11 geD CUL5 −1.3 0.11 geD TOPORS −1.5 0.11 geD CDON −1.4 0.11 geD PCMT1 −1.3 0.11 geD RPS3A −1.5 0.11 geD BMPR1A −1.3 0.11 geD PSMA1 −1.1 0.11 geD POGK −1.5 0.11 geD SSX2IP −1.1 0.11 geD SRPK1 −1.3 0.11 geD EZR −1.5 0.11 geD KLRC4 −1.4 0.11 geD PCSK9 −1.3 0.11 geD PDCD10 −1.2 0.11 geD CTNND1 −1.4 0.11 geD ARF6 −1.2 0.11 geD PPIC −1.2 0.11 geD SDCBP −1.2 0.11 geD PLG −1.2 0.11 geD GNA12 −1.2 0.11 geD ATP2C1 −1.4 0.11 geD SNRK −1.2 0.11 geD PSMF1 −1.4 0.11 geD EFNB2 −1.6 0.11 geD THBS2 −1.5 0.11 geD MRPS30 −1.4 0.11 geD JUB −1.3 0.11 geD PLAGL2 −1.4 0.11 geD IL17RD −1.8 0.11 geD CP110 −1.2 0.11 geD TRIB1 −1.4 0.11 geD OXSR1 −1.3 0.11 geD TGFB2 −1.7 0.11 geD NEDD4L −1.7 0.11 geD TAX1BP1 −1.3 0.11 geD STK3 −1.3 0.11 geD APIP −1.3 0.11 geD GCH1 −1.3 0.11 geD F2R −1.2 0.11 geD GNE −1.3 0.11 geD HSPE1 −1.3 0.11 geD PLSCR1 −1.4 0.11 geD BAG3 −1.4 0.11 geD MYH9 −1.2 0.11 geD FAM3C −1.4 0.11 geD SMOC1 −1.8 0.11 geD SLAMF7 −1.2 0.11 geD YWHAG −1.5 0.11 geD IRAK1BP1 −1.8 0.11 geD CBLB −1.3 0.11 geD PSMD14 −1.5 0.11 geD PDCL3 −1.6 0.11 geD RAB5B 1.3 0.12 geD MDM2 1.2 0.12 geD WDR92 1.3 0.12 geD BMP1 1.4 0.12 geD CHST4 1.2 0.12 geD BCL11B 1.1 0.12 geD TBXAS1 1.4 0.12 geD N-PAC 1.2 0.12 geD CD59 1.7 0.12 geD ITGA11 1.4 0.12 geD IGFBP3 1.6 0.12 geD CLDN23 1.3 0.12 geD TCTA 1.2 0.12 geD POLG 1.5 0.12 geD RAB3D 1.1 0.12 geD TRAP1 1.2 0.12 geD MAF 1.2 0.12 geD STX1A 1.3 0.12 geD VCP 1.2 0.12 geD KYNU 1.2 0.12 geD CRKL 1.3 0.12 geD CD63 1.2 0.12 geD PODXL2 1.4 0.12 geD BNIP3L 1.3 0.12 geD VCP 1.5 0.12 geD BNIP1 1.2 0.12 geD HSPB1 1.3 0.12 geD MYH9 1.2 0.12 geD CD3E 1.2 0.12 geD PLG 1.2 0.12 geD HTT 1.6 0.12 geD DCHS1 1.3 0.12 geD AQP3 1.1 0.12 geD PDPK1 1.3 0.12 geD TAF8 1.3 0.12 geD B3GNTL1 1.3 0.12 geD C8G 1.3 0.12 geD SIGLEC10 1.2 0.12 geD CNTFR 1.3 0.12 geD NID2 2.2 0.12 geD NME3 1.2 0.12 geD SNX2 1.9 0.12 geD COL24A1 1.3 0.12 geD CROP 1.3 0.12 geD CXCR5 1.5 0.12 geD TRIP10 1.4 0.12 geD PIN1 1.5 0.12 geD AIFM2 1.1 0.12 geD NFATC1 19.3 0.12 geD LDLRAP1 1.5 0.12 geD PSMB2 1.1 0.12 geD RIN2 1.1 0.12 geD BMPR1A 1.5 0.12 geD PKP4 −1.3 0.12 geD FUT8 −1.5 0.12 geD MLLT10 −1.2 0.12 geD CASP8AP2 −1.2 0.12 geD HES1 −1.7 0.12 geD CPLX1 −1.4 0.12 geD RNF216 −1.2 0.12 geD HDAC9 −1.1 0.12 geD SGPP1 −1.9 0.12 geD PSMD1 −1.7 0.12 geD HINT1 −2.3 0.12 geD GRAMD4 −1.2 0.12 geD JMY −1.6 0.12 geD PDGFC −1.2 0.12 geD LEPR −1.3 0.12 geD B3GNT5 −1.4 0.12 geD LDLR −1.3 0.12 geD POMP −1.3 0.12 geD BCL2A1 −1.4 0.12 geD PDCL3 −1.3 0.12 geD CXCL12 −1.3 0.12 geD MLLT10 −1.2 0.12 geD CUL2 −1.2 0.12 geD MLL5 −1.2 0.12 geD PRLR −1.3 0.12 geD IFIT5 −1.3 0.12 geD CLSTN2 −1.7 0.12 geD SH2D1A −1.2 0.12 geD HSP90AA1 −1.6 0.12 geD COL15A1 −1.4 0.12 geD KRAS −1.6 0.12 geD THYN1 −1.3 0.12 geD FASTKD5 −1.3 0.12 geD BSCL2 1.6 0.13 geD RAD51 1.2 0.13 geD PCDHA1 1.2 0.13 geD FSCN1 1.2 0.13 geD DBN1 1.4 0.13 geD GDF3 1.3 0.13 geD CCL21 1.5 0.13 geD EDA 1.1 0.13 geD S100A9 1.4 0.13 geD ZNF346 1.3 0.13 geD MYBPH 1.1 0.13 geD PRKCDBP 1.3 0.13 geD MUC5B 1.4 0.13 geD CCND1 1.2 0.13 geD EPO 1.2 0.13 geD FAT1 1.4 0.13 geD DBNL 1.2 0.13 geD RAE1 1.3 0.13 geD NRG1 17.7 0.13 geD PDLIM7 1.3 0.13 geD ZBP1 1.4 0.13 geD TSTA3 1.2 0.13 geD SCFD2 1.3 0.13 geD SOCS1 6.1 0.13 geD PTPRF 1.5 0.13 geD ESR1 1.2 0.13 geD CAT 1.4 0.13 geD FOXO1 1.3 0.13 geD IGF2 1.3 0.13 geD MARK4 1.1 0.13 geD SNAPIN 1.3 0.13 geD ADAMTS7 1.2 0.13 geD HLA-DMB 1.2 0.13 geD ALG9 1.2 0.13 geD EXTL1 1.7 0.13 geD ATL1 1.5 0.13 geD RAC2 1.2 0.13 geD HMGB3 1.2 0.13 geD SIGIRR 1.3 0.13 geD IGSF8 2.2 0.13 geD CCND3 1.3 0.13 geD ISG20L2 1.2 0.13 geD RTN3 1.2 0.13 geD CFB 1.4 0.13 geD MLF1 1.5 0.13 geD CLTCL1 1.2 0.13 geD THAP3 1.3 0.13 geD PDZD2 1.3 0.13 geD DNM2 1.2 0.13 geD GDF11 1.4 0.13 geD ARFGEF1 1.9 0.13 geD CTNNA1 1.2 0.13 geD HLA-E 1.3 0.13 geD MAPK13 1.3 0.13 geD EI24 1.4 0.13 geD FBLN5 1.3 0.13 geD FEZ1 1.4 0.13 geD DAP 1.4 0.13 geD MYEF2 −1.2 0.13 geD RAB13 −1.5 0.13 geD HIP1 −1.3 0.13 geD NPC1 −1.4 0.13 geD PDGFRL −1.2 0.13 geD MAP4K3 −1.2 0.13 geD RALA −1.1 0.13 geD SCARB2 −1.5 0.13 geD PRKAR1A −1.5 0.13 geD UBP1 −1.3 0.13 geD IFT81 −1.5 0.13 geD ZFYVE16 −1.6 0.13 geD VPS41 −1.5 0.13 geD SEMA4D −1.5 0.13 geD PDCD6IP −1.1 0.13 geD CD109 −1.7 0.13 geD GTF2H2 −1.2 0.13 geD GPR98 −2 0.13 geD TXNDC5 −1.5 0.13 geD ZC3H12A −1.7 0.13 geD PEG10 −1.2 0.13 geD GDNF −2.3 0.13 geD HMGB1 −1.5 0.13 geD GAB3 −1.3 0.13 geD CUL4A −1.3 0.13 geD CREBBP −1.2 0.13 geD RFX5 −1.2 0.13 geD BAG5 −1.4 0.13 geD PCDHB5 −1.6 0.13 geD BAG4 −1.3 0.13 geD RALB −1.6 0.13 geD RARG 1.4 0.14 geD CTSH 1.3 0.14 geD RAD52 1.7 0.14 geD MSLN 1.2 0.14 geD CD38 1.5 0.14 geD NFKBIL2 1.3 0.14 geD RHOT2 1.3 0.14 geD WWP2 1.2 0.14 geD DEDD 1.2 0.14 geD TRAF2 2.1 0.14 geD TNFRSF25 1.3 0.14 geD TREML2 1.3 0.14 geD MAPK13 1.2 0.14 geD SEMA4G 1.3 0.14 geD MAP4K4 1.3 0.14 geD MYBPC2 1.2 0.14 geD CD151 1.3 0.14 geD NRGN 1.4 0.14 geD MADD 1.2 0.14 geD MGC29506 1.5 0.14 geD BCL9L 1.2 0.14 geD HCP5 1.2 0.14 geD IL4I1 1.4 0.14 geD LTB4R2 1.3 0.14 geD LOC441795 1.2 0.14 geD CD200 1.2 0.14 geD LRIG1 1.2 0.14 geD CIAPIN1 1.4 0.14 geD RAB34 1.3 0.14 geD RIN2 1.3 0.14 geD TFDP1 2 0.14 geD EEF2 1.3 0.14 geD ALG1 1.3 0.14 geD COL7A1 1.3 0.14 geD CD37 1.2 0.14 geD HTRA2 1.3 0.14 geD CD8B 1.2 0.14 geD NPTN 1.1 0.14 geD KLF10 −1.2 0.14 geD PCDHB16 −1.3 0.14 geD TRAF7 −1.9 0.14 geD CLN3 −1.3 0.14 geD SON −1.3 0.14 geD MPZL2 −1.7 0.14 geD PSMD5 −1.2 0.14 geD NCKAP1 −1.2 0.14 geD NLRC3 −1.2 0.14 geD DLL1 −1.2 0.14 geD DHCR24 −1.4 0.14 geD C1D −1.4 0.14 geD BAALC −1.3 0.14 geD VHL −1.3 0.14 geD RAB27A −1.3 0.14 geD CBR1 −1.2 0.14 geD JAG1 −1.2 0.14 geD ADAM11 −1.3 0.14 geD PRKRIR −1.9 0.14 geD XCL1 −1.5 0.14 geD FANCI −1.4 0.14 geD FYB −1.2 0.14 geD CYCS −1.6 0.14 geD CETN2 −1.1 0.14 geD BCL11A −1.4 0.14 geD PSMC6 −1.6 0.14 geD PBX1 −1.2 0.14 geD SIRT1 −1.1 0.14 geD TBX21 −1.3 0.14 geD HOXA3 −1.5 0.14 geD LSM14A −1.3 0.14 geD TXNDC17 −2.1 0.14 geD CROP −1.5 0.14 geD HDAC5 1.2 0.15 geD MAPK7 1.3 0.15 geD ZAN 1.7 0.15 geD XRCC1 1.8 0.15 geD ITGB5 1.2 0.15 geD METTL1 1.2 0.15 geD SIPA1 1.1 0.15 geD MRC2 1.3 0.15 geD HLA-DOB 1.6 0.15 geD LRP10 1.1 0.15 geD CDKN1B 1.4 0.15 geD ARVCF 2.1 0.15 geD ITGA9 1.4 0.15 geD CD59 1.2 0.15 geD VPRBP 1.3 0.15 geD RELT 1.2 0.15 geD FCRLB 1.6 0.15 geD HSF1 1.2 0.15 geD PSMB3 1.2 0.15 geD HLA-DMB 2.4 0.15 geD FBLN7 1.2 0.15 geD KLF1 1.2 0.15 geD SH3GL3 1.3 0.15 geD PHLDA1 1.2 0.15 geD CLDN9 1.3 0.15 geD TNFRSF13C 1.2 0.15 geD PRKAR1B 1.3 0.15 geD SCFD1 −1.3 0.15 geD PAX3 −1.2 0.15 geD SWAP70 −1.3 0.15 geD MAP4K5 −1.6 0.15 geD MLL2 −1.6 0.15 geD RFFL −1.4 0.15 geD SOCS5 −1.3 0.15 geD STK4 −1.4 0.15 geD AMOTL1 −1.1 0.15 geD MLF1 −1.3 0.15 geD RACGAP1 −1.6 0.15 geD PPID −1.4 0.15 geD YWHAZ −1.4 0.15 geD GPR183 −1.2 0.15 geD SRPK2 −1.4 0.15 geD FAM19A2 −1.5 0.15 geD HSPA8 −1.3 0.15 geD CELSR1 −1.3 0.15 geD MYST4 −1.3 0.15 geD HSPA5 −1.4 0.15 geD RBM24 −1.5 0.15 geD MYST4 −1.5 0.15 geD CCL28 −1.3 0.15

APPENDIX K

TABLE S11 CNR-specific measurements DataType Name Fold-change Q-value phenoD CD4 TERM DIFF EFFECTOR 3.4 0 MEMORY phenoD CD4 EFFECTOR MEMORY 2.9 0 phenoD CD8 TERM DIFF EFFECTOR 10.9 0.01 MEMORY phenoD CD8 EFFECTOR MEMORY 4.9 0.03 phenoD NK T CELLS 2.1 0.03 phenoD CD4 2.5 0.03 phenoD CD8 3.3 0.06 phenoD CD4 NAIVE −2.3 0 phenoD CD8 NAIVE −2.3 0.01 phenoD B CELLS −1.4 0.02 pfBaselineD cd20_Unstimulated_STAT1 2.6 0 pfBaselineD cd20_Unstimulated_STAT3 4.3 0 pfBaselineD cd20_Unstimulated_STAT5 2.5 0 pfBaselineD cd4_Unstimulated_STAT1 1.1 0 pfBaselineD cd4_Unstimulated_STAT3 1.2 0 pfBaselineD cd4_Unstimulated_STAT5 1.1 0.01 pfBaselineD mono_Unstimulated_STAT1 1.1 0.02 pfBaselineD mono_Unstimulated_STAT3 1.1 0.06 pfD cd20_IFNg_STAT3 1.1 0.02 pfD cd20_IL6_STAT5 1 0.02 pfD cd20_IL7_STAT3 1.1 0.06 pfD cd20_IL7_STAT5 1.1 0.07 pfD cd20_IL10_STAT5 1 0.12 pfD mono_IL10_STAT5 1.1 0.13 pfD mono_IL21_STAT1 1 0.14 pfD mono_IL21_STAT5 1 0.15 pfD cd20_IFNa_STAT1 −4.2 0 pfD cd20_IFNa_STAT3 −6 0 pfD cd20_IFNa_STAT5 −3.7 0 pfD cd20_IFNg_STAT1 −4 0 pfD cd20_IL21_STAT1 −3.4 0 pfD cd20_IL21_STAT3 −2 0 pfD cd20_IL7_STAT1 −6.6 0 pfD cd4_IFNa_STAT1 −4.4 0 pfD cd4_IFNa_STAT3 −1.9 0 pfD cd4_IFNa_STAT5 −1.7 0 pfD cd4_IFNg_STAT1 −3.4 0 pfD cd4_IFNg_STAT3 −1.5 0 pfD cd4_IL10_STAT1 −3.3 0 pfD cd4_IL10_STAT3 −2.2 0 pfD cd4_IL21_STAT1 −1.3 0 pfD cd4_IL21_STAT3 −2 0 pfD cd4_IL21_STAT5 −2 0 pfD cd4_IL6_STAT1 −1.1 0 pfD cd4_IL6_STAT3 −11.2 0 pfD cd4_IL6_STAT5 −1.6 0 pfD cd4_IL7_STAT1 −2.3 0 pfD cd4_IL7_STAT3 −1.3 0 pfD cd4_IL7_STAT5 −1.4 0 pfD cd8_IFNa_STAT3 −1.8 0 pfD cd8_IFNa_STAT5 −1.5 0 pfD cd8_IFNg_STAT1 −2.8 0 pfD cd8_IFNg_STAT3 −1.2 0 pfD cd8_IFNg_STAT5 −1.9 0 pfD cd8_IL10_STAT1 −1.7 0 pfD cd8_IL10_STAT3 −1.4 0 pfD cd8_IL21_STAT3 −1.7 0 pfD cd8_IL21_STAT5 −1.2 0 pfD cd8_IL6_STAT1 −2.4 0 pfD cd8_IL6_STAT3 −1.3 0 pfD cd8_IL6_STAT5 −1 0 pfD cd8_IL7_STAT1 −1.2 0 pfD cd8_IL7_STAT3 −1.2 0.01 pfD cd8_IL7_STAT5 −1.2 0.01 pfD mono_IFNa_STAT1 −1.4 0.01 pfD mono_IFNa_STAT3 −1.4 0.01 pfD mono_IFNa_STAT5 −1.1 0.01 pfD mono_IFNg_STAT1 −1.2 0.02 pfD mono_IFNg_STAT3 −1.1 0.04 pfD mono_IFNg_STAT5 −1.1 0.05 pfD mono_IL10_STAT3 −1 0.07 pfD mono_IL21_STAT3 −1.1 0.07 pfD mono_IL6_STAT1 −1.1 0.09 pfD mono_IL6_STAT3 −1 0.11 pfD mono_IL7_STAT5 −1.1 0.14 cytM RANTES −1.3 0.15 geD FKBP1A 1.8 0.07 geD TOLLIP 2.1 0.07 geD RIMS4 1.5 0.07 geD CAV3 2.1 0.07 geD HSPA8 2.3 0.07 geD AIRE 1.4 0.07 geD NEIL3 1.5 0.07 geD INHBC 1.9 0.07 geD GH1 2.2 0.08 geD DUB3 2.3 0.09 geD ICOSLG 1.6 0.1 geD HIP1 1.5 0.1 geD ISLR2 1.9 0.1 geD MYBPC3 1.5 0.1 geD MUC5AC 1.5 0.1 geD DSC2 3 0.1 geD GREM2 1.4 0.11 geD MNT 2 0.11 geD ELN 2.1 0.11 geD PXN 1.3 0.11 geD CTSE 1.3 0.11 geD BAG3 1.5 0.12 geD SORT1 1.6 0.12 geD CTSB 1.8 0.13 geD ICAM5 2.9 0.14 geD YWHAZ 1.2 0.14 geD SBDS 1.5 0.14 geD CLN3 1.5 0.14 geD DOCK3 2 0.15 geD SERPING1 −1.6 0.03 geD ICA1 −1.6 0.07 geD DNASE1 −1.5 0.07 geD CASQ1 −1.4 0.07 geD F5 −1.5 0.07 geD LENG1 −1.4 0.07 geD PGM5 −1.4 0.07 geD EP300 −1.6 0.07 geD DGKE −1.5 0.07 geD IGFALS −1.6 0.07 geD MYL10 −1.6 0.07 geD CCL26 −1.4 0.07 geD MYC −1.5 0.07 geD MASP1 −1.4 0.07 geD IGF1R −1.6 0.07 geD THBS1 −1.4 0.07 geD TNNC2 −1.3 0.07 geD ZNF346 −1.4 0.07 geD LEFTY1 −1.4 0.07 geD DCBLD1 −1.6 0.07 geD MARK2 −1.4 0.07 geD 3-Sep −1.4 0.07 geD CBLB −1.4 0.07 geD SIX4 −1.5 0.07 geD PIK3R2 −1.5 0.07 geD CAMK1G −1.4 0.08 geD ARHGDIA −1.4 0.08 geD MIF −1.4 0.08 geD SLIT2 −1.3 0.08 geD XRCC6BP1 −1.4 0.08 geD TEC −1.3 0.08 geD BTG1 −1.4 0.08 geD LPP −1.5 0.08 geD MARK1 −1.3 0.08 geD LAMB2 −1.4 0.09 geD HIP1 −1.3 0.09 geD AR −1.3 0.09 geD BCL2L2 −1.4 0.09 geD SCD5 −1.3 0.09 geD CD1B −1.4 0.1 geD TNFRSF13B −1.3 0.1 geD EDNRA −1.4 0.1 geD SKAP2 −1.4 0.1 geD LMLN −1.3 0.1 geD TRAF7 −1.5 0.1 geD SFRS17A −1.5 0.1 geD COL6A1 −1.3 0.1 geD HSPB1 −1.7 0.1 geD NFE2L2 −1.5 0.1 geD HAPLN3 −1.4 0.1 geD C1QTNF2 −1.2 0.1 geD SYNJ2BP −1.3 0.1 geD NPNT −1.4 0.1 geD ERCC5 −1.4 0.1 geD CUL4A −1.4 0.1 geD KEL −1.3 0.1 geD PSMA5 −1.4 0.1 geD SOD2 −1.3 0.1 geD ARHGDIA −1.5 0.1 geD RAB22A −1.4 0.11 geD MAGED1 −1.3 0.11 geD LTBP2 −1.3 0.11 geD PPP1R13B −1.3 0.11 geD ULBP2 −1.4 0.11 geD ATP2A1 −1.4 0.12 geD BAT1 −1.5 0.12 geD CSNK1E −1.3 0.12 geD NLGN3 −1.4 0.12 geD ITGA9 −1.5 0.12 geD XKR3 −1.5 0.12 geD FMOD −1.4 0.12 geD CDC42SE2 −1.3 0.12 geD ALCAM −1.3 0.12 geD FN1 −1.4 0.12 geD RIPK1 −1.4 0.12 geD CDH16 −1.3 0.12 geD STK17A −1.2 0.12 geD TXLNA −1.3 0.12 geD HESX1 −1.3 0.12 geD COL6A1 −1.3 0.13 geD SGPL1 −1.7 0.13 geD PDLIM7 −1.5 0.13 geD FUT3 −1.2 0.13 geD MSN −1.4 0.13 geD CLN8 −1.3 0.13 geD PLDN −1.4 0.13 geD PLD1 −1.4 0.13 geD MYST4 −1.4 0.13 geD BLID −1.5 0.13 geD BCL6B −1.4 0.13 geD CNTFR −1.2 0.13 geD COL24A1 −1.3 0.13 geD SH3GL2 −1.3 0.14 geD GSG2 −1.3 0.14 geD BAALC −1.2 0.14 geD ADAL −1.5 0.14 geD BDNF −2 0.14 geD WISP1 −1.4 0.14 geD BCL7A −1.3 0.14 geD CDC2L2 −1.2 0.14 geD NCAM1 −1.3 0.14 geD CEACAM5 −1.3 0.14 geD CD96 −1.4 0.14 geD EMILIN1 −1.3 0.14 geD HAPLN4 −1.4 0.14 geD TXLNA −1.4 0.14 geD VNN1 −1.4 0.15 geD C1QTNF1 −1.3 0.15 geD MMP12 −1.5 0.15

APPENDIX L

TABLE S12 Fold-change - response classification results condition maxFold Unsti

FC.di

flDR

FdiffDR

hMFI

classify notes Classification of aging associated cytokine response assays (q < 0.15) cd20_IFNg_STAT

1.1 1 0 1 0 1 Baseline Defect cd20_IL7_STAT3 1.2 1 0 0 0 1 Baseline Defect cd4_IFNa_STAT1 6.3 1 1 0 0 0 Baseline Defect cd4_IFNa_STAT3 3.8 1 1 0 1 0 Baseline Defect cd4_IFNg_STAT1 1.6 1 0 0 1 1 Baseline Defect cd4_IL10_STAT1 2.2 1 0 1 0 1 Baseline Defect cd4_IL10_STAT3 6.0 1 1 0 1 0 Baseline Defect cd4_IL21_STAT1 1.6 1 0 1 0 1 Baseline Defect cd4_IL21_STAT5 1.5 1 0 1 1 0 Baseline Defect cd4_IL7_STAT5 5.0 1 1 1 0 0 Baseline Defect cd8_IL10_STAT1 1.9 1 0 1 0 1 Baseline Defect cd8_IL21_STAT5 1.4 1 0 1 1 0 Baseline Defect cd8_IL7_STAT1 1.2 1 0 1 0 1 Baseline Defect cd8_IL7_STAT3 1.4 1 0 0 0 1 Baseline Defect cd20_IFNa_STAT

4.2 1 1 0 0 1 Baseline Resistance Defect cd20_IFNa_STAT

2.8 1 1 1 1 1 Baseline Resistance Defect cd20_IFNa_STAT

1.7 1 1 1 0 1 Baseline Resistance Defect cd4_IFNa_STAT5 3.4 1 1 1 0 1 Baseline Resistance Defect cd4_IL21_STAT3 5.5 1 1 1 1 0 Baseline Resistance Defect cd4_IL6_STAT1 6.0 1 1 0 1 1 Baseline Resistance Defect cd4_IL6_STAT3 5.9 1 1 1 1 1 Baseline Resistance Defect cd4_IL6_STAT5 2.1 1 1 1 1 1 Baseline Resistance Defect cd4_IL7_STAT3 1.3 1 1 1 0 1 Baseline Resistance Defect cd8_IFNa_STAT1 7.2 1 1 0 0 1 Baseline Resistance Defect cd8_IFNa_STAT3 3.7 1 1 1 1 1 Baseline Resistance Defect cd8_IFNa_STAT5 2.8 1 1 0 0 1 Baseline Resistance Defect cd8_IFNg_STAT1 1.5 1 1 0 1 1 Baseline Resistance Defect cd8_IL21_STAT1 1.7 1 1 1 1 1 Baseline Resistance Defect cd8_IL6_STAT1 4.7 1 1 0 1 1 Baseline Resistance Defect cd8_IL6_STAT3 5.8 1 1 0 1 1 Baseline Resistance Defect cd8_IL6_STAT5 1.5 1 1 1 1 0 Baseline Resistance Defect mono_IFNa_STA

3.1 0 1 0 0 1 Resistance Defect mono_IFNa_STA

2.3 0 1 0 0 1 Resistance Defect mono_IFNa_STA

1.5 0 1 1 0 1 Resistance Defect mono_IL6_STAT

2.3 0 1 1 1 1 Resistance Defect mono_IFNg_STA

1.5 0 0 1 1 0 Unknown mono_IFNg_STA

1.6 0 0 1 0 0 Unknown mono_IL6_STAT

1.2 0 0 0 0 1 Unknown mono_IL7_STAT

1.3 0 0 1 0 0 Unknown Classification of cytokine response assays not shown to be different in the aging in the general (29 individuals) population cd20_IFNg_STAT

1.4 1 0 1 0 1 Baseline Defect cd20_IL10_STAT

1.7 1 0 1 0 1 Baseline Defect cd20_IL10_STAT

1.3 1 0 1 0 1 Baseline Defect cd20_IL21_STAT

1.4 1 0 1 0 1 Baseline Defect cd20_IL6_STAT1 1.2 1 0 1 1 1 Baseline Defect cd20_IL6_STAT5 1.3 1 0 1 0 1 Baseline Defect cd20_IL7_STAT5 1.3 1 0 1 0 1 Baseline Defect cd4_IL10_STAT5 1.5 1 0 1 0 1 Baseline Defect cd4_IL7_STAT1 1.3 1 0 1 0 1 Baseline Defect cd8_IFNg_STAT3 1.2 1 0 0 0 1 Baseline Defect cd8_IFNg_STAT5 1.2 1 0 1 0 1 Baseline Defect cd8_IL10_STAT5 1.3 1 0 1 0 1 Baseline Defect cd20_IFNg_STAT

3.5 1 0 1 0 1 Baseline Defect cd20_IL10_STAT

5.1 1 0 1 0 0 Baseline Defect cd20_IL21_STAT

1.5 1 0 0 0 1 Baseline Defect cd20_IL7_STAT1 1.2 1 0 1 0 1 Baseline Defect cd4_IFNg_STAT3 1.1 1 0 0 0 1 Baseline Defect cd4_IFNg_STAT5 1.2 1 0 1 0 1 Baseline Defect cd8_IL10_STAT3 6.1 1 0 1 0 0 Baseline Defect cd8_IL21_STAT3 5.8 1 1 1 0 0 Baseline Defect cd20_IL6_STAT3 1.3 1 1 1 1 1 Baseline Resistance Defect cd20_IL21_STAT

3.7 1 1 1 0 1 Baseline Resistance Defect cd8_IL7_STAT5 3.9 1 1 1 0 1 Baseline Resistance Defect mono_IL21_STA

1.7 0 1 1 0 1 Resistance Defect mono_IL10_STA

1.9 0 0 1 0 1 Unknown mono_IL10_STA

1.4 0 0 1 0 1 Unknown mono_IL21_STA

1.4 0 0 0 0 1 Unknown mono_IL21_STA

1.2 0 0 1 0 1 Unknown mono_IL6_STAT

1.2 0 0 1 0 1 Unknown mono_IL7_STAT

1.2 0 0 0 0 1 Unknown mono_IL7_STAT

1.2 0 0 0 0 1 Unknown mono_IFNg_STA

3.8 0 0 1 0 0 Unknown mono_IL10_STA

5.4 0 0 1 1 0 Unknown

indicates data missing or illegible when filed 

1. A method of diagnosing a state of immune function in an individual, said method comprising (a) obtaining an immune system profile from said individual in comparison to control individuals, said immune profile comprising measurements of immune cell subset frequencies, gene expression, cytokine levels, chemokine levels, baseline phosphorylation levels of proteins and magnitude of change in phosphorylation level of said proteins in response to stimulation with cytokines (‘cytokine response’); (b) physical transformation of said immune system profile into information for graphical display or output to a computer-readable medium, computer or computer network.
 2. The method of claim 1, wherein said individual is at least 60 years old.
 3. The method of claim 1, wherein said cell subset frequencies are characterized by an age-associated change.
 4. The method of claim 3, wherein the age-associated change is a decrease in the frequency of CD8⁺ naïve cells.
 5. The method of claim 3, wherein the age-associated change is an increase in the frequency of monocytes.
 6. The method of claim 3, wherein the age-associated change is an increase in the frequency of CD8⁺ and CD4⁺D28⁻ naïve cells.
 7. The method of claim 3, wherein the age-associated change is an increase in the frequency of natural killer T (NKT) cells.
 8. The method of claim 3, wherein the age-associated change is an increase in the frequency of CD8⁺ and CD4⁺ memory T cells.
 9. The method of claim 1, wherein said proteins are STAT proteins.
 10. The method of claim 9, wherein said STAT proteins are STAT1, STAT3 and STAT5.
 11. The method of claim 9, wherein said STAT proteins are STAT1, STAT3 or STAT5.
 12. The method of claim 1, wherein said cytokine response is measured upon stimulation with IFN-α, IFN-γ, IL6, IL7, IL10 or IL21.
 13. The method of claim 1, wherein said measurements of cytokine levels relate to one or more of the following cytokines: eotaxin, IFN-γ, IL-7, MCP-1, MCP-3, IL-12-P70, IL-17, IL-4, TGF-α, IP10, TNF-α, IFNA2, IL-5.
 14. The method of claim 1, wherein said measurements of chemokine levels relate to one or more of the following chemokines: CXCL1, CXCL5.
 15. The method of claim 1, wherein said measurements of gene expression relate to one or more of the genes from Tables S2, S9, S10 and S11.
 16. A method of diagnosing impaired immune function in an individual in comparison to control individuals, said method comprising (a) obtaining an immune system profile from said individual, said immune profile comprising measurements of baseline phosphorylation of STAT proteins before stimulation with cytokines and measurements of fold-change of phosphorylation of STAT proteins following stimulation with cytokines (‘cytokine response’) in multiple cell-types, (b) analyzing said measurements, wherein, decreased fold-change following stimulation with cytokines indicate a cytokine non-response in said individual, and a cytokine non-response indicates impaired immune function in said individual; and wherein non-increased baseline phosphorylation before said stimulation with cytokines and non-decreased fold-change following stimulation with cytokines indicate a cytokine response in said individual, and a cytokine response indicates non-impaired immune function in said individual. (b) physical transformation of said immune system profile into information for graphical display or output to a computer-readable medium, computer or computer network.
 17. The method of claim 16, wherein said STAT proteins are STAT1, STAT3 and STAT5.
 18. The method of claim 16, wherein said STAT proteins are STAT1, STAT3 or STAT5.
 19. The method of claim 16, wherein said cytokine response is measured upon stimulation with IFN-α, IFN-γ, IL6, IL7, IL10 or IL21.
 20. The method of claim 16, wherein said individual is at least 60 years old.
 21. A method of classifying individuals in individuals with impaired immune function and individuals with non-impaired immune function in comparison to control individuals, said method comprising (a) obtaining an immune system profile from said individuals, said immune profile comprising measurements of baseline phosphorylation of STAT proteins before stimulation with cytokines and measurements of fold-change of phosphorylation of STAT proteins following stimulation with cytokines (‘cytokine response’) in multiple cell-types, (b) analyzing said measurements, wherein increased baseline phosphorylation before said stimulation with cytokines and decreased fold-change following stimulation with cytokines indicate a cytokine non-response in said individuals, and a cytokine non-response indicates impaired immune function in said individuals; and wherein non-increased baseline phosphorylation before said stimulation with cytokines and non-decreased fold-change following stimulation with cytokines indicate a cytokine response in said individuals, and a cytokine response indicates non-impaired immune function in said individuals. (c) physical transformation of said immune system profile into information for graphical display or output to a computer-readable medium, computer or computer network.
 22. The method of claim 21, wherein said STAT proteins are STAT1, STAT3 and STAT5.
 23. The method of claim 21, wherein said STAT proteins are STAT1, STAT3 or STAT5.
 24. The method of claim 21, wherein said cytokine response is measured upon stimulation with IFN-α, IFN-γ, IL6, IL7, IL10 or IL21.
 25. A method of assessing immune function in an individual in comparison to control individuals, said method comprising (a) obtaining an immune system profile from said individual, said immune profile comprising measurements of immune cell subset frequencies, gene expression, cytokine levels, chemokine levels and signaling responses to stimulation with cytokines (‘cytokine response’); (b) physical transformation of said immune system profile into information for graphical display or output to a computer-readable medium, computer or computer network.
 26. The method of claim 25, wherein said individual is at least 60 years old.
 27. A method of assessing immune function in an individual in comparison to control individuals, said method comprising (a) obtaining an immune system profile from said individual, said immune profile comprising measurements of baseline phosphorylation of STAT proteins before stimulation with cytokines and measurements of fold-change of phosphorylation of STAT proteins following stimulation with cytokines (‘cytokine response’) in multiple cell-types, (b) analyzing said measurements, wherein, in comparison to said control individual, decreased fold-change following stimulation with cytokines indicate a cytokine non-response in said individual, and a cytokine non-response indicates impaired immune function in said individual; and wherein, in comparison to said control individual, non-decreased fold-change following stimulation with cytokines indicate a cytokine response in said individual, and a cytokine response indicates non-impaired immune function in said individual. (c) physical transformation of said immune system profile into information for graphical display or output to a computer-readable medium, computer or computer network.
 28. The method of claim 27, wherein said STAT proteins are STAT1, STAT3 and STAT5.
 29. The method of claim 27, wherein said STAT proteins are STAT1, STAT3 or STAT5.
 30. The method of claim 27, wherein said cytokine response is measured upon stimulation with IFN-α, IFN-γ, IL6, IL7, IL10 or IL21.
 31. A method of assessing immune function in an individual in comparison to a control individual, said method comprising (a) obtaining an immune system profile from said individual in comparison to a control individual, said immune profile comprising measurements of baseline phosphorylation of STAT proteins in multiple cell-types; (b) analyzing said measurements, wherein, in comparison to said control individual, increased baseline phosphorylation indicates a cytokine non-response in said individual, and a cytokine non-response indicates impaired immune function in said individual; and wherein, in comparison to said control individual, non-increased baseline phosphorylation indicates a cytokine response in said individual, and a cytokine response indicates non-impaired immune function in said individual. (c) physical transformation of said immune system profile into information for graphical display or output to a computer-readable medium, computer or computer network.
 32. The method of claim 31, wherein said STAT proteins are STAT1, STAT3 and STAT5.
 33. The method of claim 31, wherein said STAT proteins are STAT1, STAT3 or STAT5.
 34. The method of claim 31, wherein said cytokine response is measured upon stimulation with IFN-α, IFN-γ, IL6, IL7, IL10 or IL21. 